YKL40/Integrin ß4 Axis Induced by the Interaction between Cancer Cells and Tumor-Associated Macrophages Is Involved in the Progression of High-Grade Serous Ovarian Carcinoma.

Macrophages in the tumor microenvironment, termed tumor-associated macrophages (TAMs), promote the progression of various cancer types. However, many mechanisms related to tumor-stromal interactions in epithelial ovarian cancer (EOC) progression remain unclear. High-grade serous ovarian carcinoma (HGSOC) is the most malignant EOC subtype. Herein, immunohistochemistry was performed on 65 HGSOC tissue samples, revealing that patients with a higher infiltration of CD68+, CD163+, and CD204+ macrophages had a poorer prognosis. We subsequently established an indirect co-culture system between macrophages and EOC cells, including HGSOC cells. The co-cultured macrophages showed increased expression of the TAM markers CD163 and CD204, and the co-cultured EOC cells exhibited enhanced proliferation, migration, and invasion. Cytokine array analysis revealed higher YKL40 secretion in the indirect co-culture system. The addition of YKL40 increased proliferation, migration, and invasion via extracellular signal-regulated kinase (Erk) signaling in EOC cells. The knockdown of integrin ß4, one of the YKL40 receptors, suppressed YKL40-induced proliferation, migration, and invasion, as well as Erk phosphorylation in some EOC cells. Database analysis showed that high-level expression of YKL40 and integrin ß4 correlated with a poor prognosis in patients with serous ovarian carcinoma. Therefore, the YKL40/integrin ß4 axis may play a role in ovarian cancer progression.

Drug-Loaded Nanocarriers Composed of Cholesteryl Oleate Crystal Cores and Multiple-Nanosheet Shells of γ-Cyclodextrin Inclusion Complex Crystals.

In this study, we prepared drug-loaded nanocarriers made of cholesteryl oleate (ChO) and γ-cyclodextrin (γ-CD). A nanosuspension (nanosuspension-I, NS-I) containing nanoparticles with a mean size of approximately 170 nm was obtained through the solvent-diffusion method using ethanol. A second nanosuspension (nanosuspension-II, NS-II), which was prepared by freeze-drying and redispersion of NS-I, exhibited an increased particle size of approximately 210 nm. Cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM) force-distance curves indicated that the nanoparticles in NS-I were oblong and soft. However, those in NS-II were angular and stiff, and, interestingly, multiple nanosheets covered the solid-liquid interface. Synchrotron wide-angle X-ray diffraction (WAXD) analysis of NS-II indicated that the nanoparticles in it had a core-shell structure, where the ChO crystal in the inner core was covered by multiple nanosheets of ChO/γ-CD inclusion complex crystals. The X-ray peak analysis suggested that the γ-CD columns of the nanosheets were vertically stacked onto the ChO crystal interface. It was found that the nanosheets on the nanoparticle interface were formed during the freezing process. A model drug carbamazepine (CBZ) was loaded into the ChO/γ-CD nanoparticles by pre-dissolving CBZ in ethanol during the solvent-diffusion process. Cryo-TEM, 1H NMR, ζ-potentials, and synchrotron WAXD indicated that CBZ was unexpectedly loaded into the shell as a CBZ/γ-CD inclusion complex crystalline nanosheet. The specific nanosheet structure, where ChO and CBZ coexisted in the same crystal of γ-CD, could achieve CBZ loading in the nanoparticles. ChO/γ-CD nanoparticles with the unique core-shell structure are expected to perform as practical carriers for drug delivery.

From understanding others' needs to prosocial action: Motor and social abilities promote infants' helping.

In the present study, we test the main hypothesis that infants' understanding of others' needs translates into helping behavior, when critical motor and social competencies have emerged, early in the second year. We assessed the understanding of others' needs in an eye-tracking paradigm and the helping behavior of 10- (n = 41) and 16-month-olds (n = 37). Furthermore, we assessed the motor and social abilities of 16-month-olds. Critically, while infants understood others' needs already at 10 months, fine motor and social interaction skills moderated the link between infants' prosocial understanding and helping behavior at 16 months. This provides first evidence that infants' helping behavior relates to their understanding of others' needs. Furthermore, we found that fine motor, gross motor, and social interaction skills predicted early helping behavior by themselves. These findings highlight that the emergence of infants' helping behavior is the result of a developmental system that includes infants' understanding of others' needs and also their motor and social competencies. The link between infants' understanding of others' needs and their early helpful actions provide further support for the prosocial nature of early helping behavior.

AREG Upregulation in Cancer Cells via Direct Interaction with Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression Through EGFR-Erk/p38 MAPK Signaling.

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and significantly contribute to the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Our previous study established a direct co-culture system of human bone marrow-derived mesenchymal stem cells (progenitors of CAFs) and ESCC cell lines, which facilitates the generation of CAF-like cells and enhances malignancy in ESCC cells. In this study, we further elucidated the mechanism by which CAFs promote ESCC progression using cDNA microarray analysis of monocultured ESCC cells and those co-cultured with CAFs. We observed an increase in the expression and secretion of amphiregulin (AREG) and the expression and phosphorylation of its receptor EGFR in co-cultured ESCC cells. Moreover, AREG treatment of ESCC cells enhanced their survival and migration via the EGFR-Erk/p38 MAPK signaling pathway. Immunohistochemical analysis of human ESCC tissues showed a positive correlation between the intensity of AREG expression at the tumor-invasive front and the expression level of the CAF marker FAP. Bioinformatics analysis confirmed significant upregulation of AREG in ESCC compared with normal tissues. These findings suggest that AREG plays a crucial role in CAF-mediated ESCC progression and could be a novel therapeutic target for ESCC.

Formation mechanism of amorphous drug nanoparticles using the antisolvent precipitation method elucidated by varying the preparation temperature.

The present study focuses on the effect of the preparation temperature on the physicochemical properties of amorphous drug nanoparticles to clarify their formation mechanism. Amorphous glibenclamide (GLB) nanoparticles were prepared at 4-40 °C using two antisolvent precipitation methods. In method A, N,N-dimethylformamide (DMF) solution of GLB was added to an aqueous solution containing hydroxypropyl methylcellulose (HPMC) to obtain nano-A suspensions. In method B, nano-B suspensions were obtained by adding DMF solution containing both GLB and HPMC into water. When the preparation temperature was above 25 °C, nano-A and nano-B showed similar HPMC compositions. However, nano-B contained a large amount of HPMC compared to nano-A at temperatures below 20 °C. The glassy nature of the nanoparticle cores restricts the diffusion of HPMC from amorphous GLB nanoparticles to the aqueous phase, indicating that the glass transition temperature (Tg) of neat amorphous GLB (73 °C) would be considerably decreased owing to the nanosizing and water sorption of amorphous GLB. The physical stability of amorphous GLB nanoparticles was improved with increased HPMC in the nanoparticles. Thus, setting the preparation temperature by considering the Tg of the antisolvent-saturated amorphous drug nanoparticles is essential to develop stable amorphous drug nanoparticles.

A case of peripancreatic plexiform schwannoma.

BACKGROUND: Plexiform schwannoma is one of the least common variants of schwannoma, accounting for only 5% of all schwannoma cases. It generally occurs in the skin and subcutaneous tissues and is uncommon in deep soft tissue or viscera. We present an extremely rare case of plexiform schwannoma arising from the peripancreatic plexus. CASE PRESENTATION: A 29-year-old man presented with hyperglycemia detected during a medical checkup. He was diagnosed with type 1 diabetes based on the clinical findings and laboratory tests. During the diagnostic process for diabetes, a 2.5 cm mass was incidentally detected in the pancreas by abdominal ultrasound. Contrast-enhanced computed tomography revealed a mass that was gradually enhanced at the body and tail of the pancreas. Magnetic resonance imaging revealed low signal intensity of the mass on T1-weighted images and high signal intensity on T2-weighted and diffusion-weighted images. Magnetic resonance cholangiopancreatography showed no abnormal findings in the main pancreatic duct. Endoscopic ultrasonography (EUS) showed a lobulated, low-echoic mass with a clear boundary. EUS-guided fine needle biopsy was performed, and spindle-shaped cells that were diffusely immunopositive for S-100 and negative for c-kit and desmin were detected, resulting in a diagnosis of a neurogenic tumor arising from the pancreas or the peripancreatic nerve plexus. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. Although the tumor was connected to the splenic plexus, the splenic artery could be divided along its adventitial plane. Macroscopic findings of the excised tumor consisted of multiple yellowish-white nodules, and its histopathological features were consistent with plexiform schwannoma. There was no pancreatic tissue on the dorsal surface of the tumor, which suggested that the tumor arose from the peripancreatic nerve plexus. CONCLUSIONS: The findings documented herein can aid in the differential diagnosis of peripancreatic schwannoma and in planning appropriate treatment.

[Think about a Pharmacist/Pharmacy in the Insurance Pharmacy-Things to Consider in the Field].

About two years have passed since the formal establishment of the category "family pharmacist" in Japan's revision of dispensing fees. In the pharmacy vision for patients, many problems were raised among the category of "family pharmacists" or "family pharmacies". Furthermore, in the future restructuring of pharmacy practices, by 2025 all pharmacies are to serve as "family pharmacies", and by 2035 they will exercise their family pharmacy function in daily living areas. In order to demonstrate the "family function", home medical care and outreach type health support etc. will be required, not only from conventional pharmacy work but also in outside (off-site) pharmacy activities. Therefore, future pharmacies need to gain the confidence of their local communities, such as in active collaboration with multi-occupational physicians and healthcare providers, work with multi-occupations in general, participation in local activities, and so on. Therefore, I would like to introduce activities that I am actually doing to this end, such as at-home activities, community activities and cooperation with multiple occupations.