Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition

Cell competition is a biological process by which unfit cells are eliminated from “cell society.” We previously showed that cultured mammalian epithelial Madin‐Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by “normal” MDCK cells. However, the molecular mechanism underlying the elimination of active YAP‐expressing cells was unknown. Here, we used high‐throughput chemical compound screening to identify cyclooxygenase‐2 (COX‐2) as a key molecule triggering cell competition. Our work shows that COX‐2‐mediated PGE₂ secretion engages its receptor EP2 on abnormal and nearby normal cells. This engagement of EP2 triggers downstream signaling via an adenylyl cyclase‐cyclic AMP‐PKA pathway that, in the presence of active YAP, induces E‐cadherin internalization leading to apical extrusion. Thus, COX‐2‐induced PGE₂ appears a warning signal to both abnormal and surrounding normal cells to drive cell competition.     

Do Cancer Patients Tweet? Examining the Twitter Use of Cancer Patients in Japan

Background

Twitter is an interactive, real-time media that could prove useful in health care. Tweets from cancer patients could offer insight into the needs of cancer patients.

Objective

The objective of this study was to understand cancer patients’ social media usage and gain insight into patient needs.

Methods

A search was conducted of every publicly available user profile on Twitter in Japan for references to the following: breast cancer, leukemia, colon cancer, rectal cancer, colorectal cancer, uterine cancer, cervical cancer, stomach cancer, lung cancer, and ovarian cancer. We then used an application programming interface and a data mining method to conduct a detailed analysis of the tweets from cancer patients.

Results

Twitter user profiles included references to breast cancer (n=313), leukemia (n=158), uterine or cervical cancer (n=134), lung cancer (n=87), colon cancer (n=64), and stomach cancer (n=44). A co-occurrence network is seen for all of these cancers, and each cancer has a unique network conformation. Keywords included words about diagnosis, symptoms, and treatments for almost all cancers. Words related to social activities were extracted for breast cancer. Words related to vaccination and support from public insurance were extracted for uterine or cervical cancer.

Conclusions

This study demonstrates that cancer patients share information about their underlying disease, including diagnosis, symptoms, and treatments, via Twitter. This information could prove useful to health care providers.     

The migration pathway of an extracted maxillary third molar into the buccal fat pad

The migration of the maxillary third molar is one of the most critical complications that can occur during extraction, and the most frequent site of migration is the maxillary sinus. We herein report an extremely rare case in which the migrated maxillary third molar became displaced into the buccal fat pad. The pathway of migration from the original site of the tooth into the buccal space is therefore considered from the anatomical perspective in this paper.     

BIOPHARMACEUTICAL EVALUATION OF THE LIPOSOMES PREPARED BY REHYDRATION OF FREEZE-DRIED EMPTY LIPOSOMES (FDELs) WITH AN AQUEOUS SOLUTION OF A DRUG

We have evaluated a method for preparation of a dispersion of liposomes encapsulating a drug, namely rehydration of freeze-dried empty (not containing drug) liposomes with an aqueous drug solution (FDEL method). In the present study, we characterized and compared this method with the conventional method using a lipid composition of DPPC–DPPG–cholesterol in a molar ratio of 27:3:20. Two hydrophilic compounds, [³H]-inulin and [³H]-mannitol, were used as model drugs. Liposomal preparations by the FDEL method had an encapsulation efficiency of 2.9 and 6.7% for [³H]-inulin and [³H]-mannitol, respectively, when rehydrated and incubated at 70 °C. Since non-specific adsorption of these markers to liposomal membrane is negligible, this method produces liposomes which encapsulate a drug in the intravesicular space. One-tenth of the marker encapsulated in the liposomes prepared by the FDEL method (F-liposomes) was released very rapidly on incubation with rat plasma, followed by the slow release of the remaining fraction thereafter. No such rapid-release phase was observed for the liposomes prepared by the conventional method (C-liposomes). This suggests the existence of two types of encapsulation, loose encapsulation and tight encapsulation, in F-liposomes at least. Pharmacokinetic parameters of marker encapsulated tightly in F-liposomes were comparable to those in C-liposomes. It is likely that amphipathic drugs such as doxorubicin are incorporated into liposomes more easily than inulin and mannitol when formulated by the FDEL method. These results therefore suggest that the FDEL method is useful in the preparation of a liposomal formulation of a drug.     

Properties of Magnetic Garnet Films for Flexible Magneto-Optical Indicators Fabricated by Spin-Coating Method

Non-destructive testing using a magneto-optical effect is a high-resolution non-destructive inspection technique for a metallic structure. It is able to provide high-spatial resolution images of defects. Previously, it has been difficult to fabricate flexible magneto-optical sensors because thermal treatment is necessary to crystallize the magnetic garnet. Therefore, it was not possible to apply magneto-optical imaging to complicated shapes in a test subject, such as a curved surface. In this study, we developed a new process for deposition of the magnetic garnet on the flexible substrate by applying the magnetic garnet powders that have already undergone crystallization. In this new process, as it does not require thermal treatment after deposition, flexible substrates with low heat resistance can be used. In this paper, we report our observations of the optical properties, magnetic hysteresis loop, crystallizability and density of the particles on the flexible substrate deposited by the spin-coating method.     

Neurocognitive and psychiatric disorders-related axonal degeneration in Parkinson's disease

Neurocognitive and psychiatric disorders have significant consequences for quality of life in patients with Parkinson's disease (PD). In the current study, we evaluated microstructural white matter (WM) alterations associated with neurocognitive and psychiatric disorders in PD using neurite orientation dispersion and density imaging (NODDI) and linked independent component analysis (LICA). The indices of NODDI were compared between 20 and 19 patients with PD with and without neurocognitive and psychiatric disorders, respectively, and 25 healthy controls using tract-based spatial statistics and tract-of-interest analyses. LICA was applied to model inter-subject variability across measures. A widespread reduction in axonal density (indexed by intracellular volume fraction [ICVF]) was demonstrated in PD patients with and without neurocognitive and psychiatric disorders, as compared with healthy controls. Compared with patients without neurocognitive and psychiatric disorders, patients with neurocognitive and psychiatric disorders exhibited more extensive (posterior predominant) decreases in axonal density. Using LICA, ICVF demonstrated the highest contribution (59% weight) to the main effects of diagnosis that reflected widespread decreases in axonal density. These findings suggest that axonal loss is a major factor underlying WM pathology related to neurocognitive and psychiatric disorders in PD, whereas patients with neurocognitive and psychiatric disorders had broader axonal pathology, as compared with those without. LICA suggested that the ICVF can be used as a useful biomarker of microstructural changes in the WM related to neurocognitive and psychiatric disorders in PD.     

Layer-specific dilation of penetrating arteries induced by stimulation of the nucleus basalis of Meynert in the mouse frontal cortex

To clarify mechanisms through which activation of the nucleus basalis of Meynert (NBM) increases cerebral cortical blood flow, we examined whether cortical parenchymal arteries dilate during NBM stimulation in anesthetized mice. We used two-photon microscopy to measure the diameter of single penetrating arteries at different depths (∼800 μm, layers I to V) of the frontal cortex, and examined changes in the diameter during focal electrical stimulation of the NBM (0.5 ms at 30 to 50 μA and 50 Hz) and hypercapnia (3% CO₂ inhalation). Stimulation of the NBM caused diameter of penetrating arteries to increase by 9% to 13% of the prestimulus diameter throughout the different layers of the cortex, except at the cortical surface and upper part of layer V, where the diameter of penetrating arteries increased only slightly during NBM stimulation. Hypercapnia caused obvious dilation of the penetrating arteries in all cortical layers, including the surface arteries. The diameters began to increase within 1 second after the onset of NBM stimulation in the upper cortical layers, and later in lower layers. Our results indicate that activation of the NBM dilates cortical penetrating arteries in a layer-specific manner in magnitude and latency, presumably related to the density of cholinergic nerve terminals from the NBM.     

Intestinal epithelial culture under an air‐liquid interface: a tool for studying human and mouse esophagi

This study investigated whether an intestinal epithelial culture method can be applied to mouse and human esophageal cultures. The esophagi harvested from 1‐day‐old mice and adult humans were maintained in collagen gels. A commercially available culture medium for human embryonic stem cells was used for the human esophageal culture. We discovered that the intestinal epithelial culture method can be successfully applied to both mouse and human esophageal cultures. The long‐term cultured esophageal organoids were rod‐like luminal structures lined with myofibroblasts. We discovered that regeneration of the esophageal mucosal surface can be almost completely achieved in vitro, and the advantage of this method is that organoid cultures may be generated using host‐derived fibroblasts as a niche. This method is a promising tool for mouse and human research in intestinal biology, carcinogenesis, and regenerative medicine.