The investigation of bioactivity and mechanical properties of glass ionomer cements prepared from Al2O3-SiO2 glass and poly(γ-glutamic acid)

The glass ionomer cement as one of the dental cements has been subjected to be widespread application in restoring tooth structure. Most of glass ionomer cements employ the poly(acrylic acid) (PAA) as the liquid phase, but the presence of PAA inhibits the apatite formation on the surface in the body environment, which is an essential requirement for exhibiting bone-bonding ability (bioactivity). In this study, poly(γ-glutamic acid) (γ-PGA), a kind of biopolymer, was utilized for cement preparation. The effort of preparation parameters including the glass powders/liquid ratio (P/L) and the concentration of γ-PGA on diametral tensile strength were investigated. A maximum diametral tensile strength value of MPa was obtained when the cement sample was prepared by P/L ratio of 1 : 1 and the γ-PGA concentration of 30% after aging for 3 days. The TF-XRD patterns, SEM images, and EDX spectra suggested that the cement induced a precipitation of calcite on the surface after 7 days of immersion in stimulated body fluid (SBF), although the apatite formation was not observed. The present results suggest that the cement has potential to show bioactivity in vivo, because calcite is also reported to be bioactive

Effects of organic polymer addition in magnetite synthesis on its crystalline structure

Magnetite (Fe3O4) nanoparticles and magnetite-based inorganic–organic hybrids are attracting attention in biomedical fields as thermoseeds for hyperthermia and a contrast medium in magnetic resonance imaging. Size control of Fe3O4 thermoseeds is important as the particle size affects the heat generation properties. Fe3O4 can be easily synthesized via aqueous processes and the presence of organic substances during synthesis can affect the size and crystalline phase of the Fe3O4 formed. In this study, various polymers with different functional groups and surface charges were added to the precursor solution of Fe3O4 to clarify the relationship between the chemical structure of the organic substances and the crystal structure of Fe3O4. At first, coexistence effects of the organic substances in the solutions were clarified. As a result, crystalline Fe3O4 was precipitated even after addition of neutral polyethylene glycol and cationic poly(diallyldimethylammonium chloride). The poly(sodium-4-styrene sulfonate) addition significantly decreased the particle size, while polyacrylic acid addition inhibited Fe3O4 nucleation to afford an amorphous phase. These differences were related to the ease of complex formation from iron ions and coexisting organic polymers. In order to clarify this assumption, a modified experimental procedure was applied for the polyacrylic acid. Namely, the iron oxide precipitation by the NaOH solution was followed by the polyacrylic acid addition. Notably, Fe3O4 nucleation was not inhibited. Hence, the size and crystalline phase of the iron oxide prepared by the aqueous process were drastically affected by organic polymers

CD133 facilitates epithelial-mesenchymal transition through interaction with the ERK pathway in pancreatic cancer metastasis

BACKGROUND: Pancreatic cancer is a lethal disease due to the high incidence of metastasis at the time of detection. CD133 expression in clinical pancreatic cancer correlates with poor prognosis and metastasis. However, the molecular mechanism of CD133-regulated metastasis remains unclear. In recent years, epithelial-mesenchymal transition (EMT) has been linked to cancer invasion and metastasis. In the present study we investigated the role of CD133 in pancreatic cancer metastasis and its potential regulatory network. METHODS: A highly migratory pancreatic cancer cell line, Capan1M9, was established previously. After shRNA was stable transducted to knock down CD133 in Capan1M9 cells, gene expression was profiled by DNA microarray. Orthotopic, splenic and intravenous transplantation mouse models were set up to examine the tumorigenesis and metastatic capabilities of these cells. In further experiments, real-time RT-PCR, Western blot and co-immunoprecipitate were conducted to evaluate the interactions of CD133, Slug, N-cadherin, ERK1/2 and SRC. RESULTS: We found that CD133(+) human pancreatic cancer cells were prone to generating metastatic nodules in in vivo models using immunodeficient mice. In contrast, CD133 knockdown suppressed cancer invasion and metastasis in vivo. Gene profiling analysis suggested that CD133 modulated mesenchymal characteristics including the expression of EMT-related genes, such as Slug and N-cadherin. These genes were down-regulated following CD133 knockdown. Moreover, CD133 expression could be modulated by the extracellular signal-regulated kinase (ERK)1/2 and SRC signaling pathways. The binding of CD133 to ERK1/2 and SRC acts as an indispensable mediator of N-cadherin expression. CONCLUSIONS: These results demonstrate that CD133 plays a critical role in facilitating the EMT regulatory loop, specifically by upregulating N-cadherin expression, leading to the invasion and metastasis of pancreatic cancer cells. Our study provides a novel insight into the function of CD133 in the EMT program and a better understanding of the mechanism underlying the involvement of CD133 in pancreatic cancer metastasis

Effects of organic polymer addition in magnetite synthesis on its crystalline structure

Magnetite (Fe3O4) nanoparticles and magnetite-based inorganic–organic hybrids are attracting attention in biomedical fields as thermoseeds for hyperthermia and a contrast medium in magnetic resonance imaging. Size control of Fe3O4 thermoseeds is important as the particle size affects the heat generation properties. Fe3O4 can be easily synthesized via aqueous processes and the presence of organic substances during synthesis can affect the size and crystalline phase of the Fe3O4 formed. In this study, various polymers with different functional groups and surface charges were added to the precursor solution of Fe3O4 to clarify the relationship between the chemical structure of the organic substances and the crystal structure of Fe3O4. At first, coexistence effects of the organic substances in the solutions were clarified. As a result, crystalline Fe3O4 was precipitated even after addition of neutral polyethylene glycol and cationic poly(diallyldimethylammonium chloride). The poly(sodium-4-styrene sulfonate) addition significantly decreased the particle size, while polyacrylic acid addition inhibited Fe3O4 nucleation to afford an amorphous phase. These differences were related to the ease of complex formation from iron ions and coexisting organic polymers. In order to clarify this assumption, a modified experimental procedure was applied for the polyacrylic acid. Namely, the iron oxide precipitation by the NaOH solution was followed by the polyacrylic acid addition. Notably, Fe3O4 nucleation was not inhibited. Hence, the size and crystalline phase of the iron oxide prepared by the aqueous process were drastically affected by organic polymers

Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma

成人T細胞白血病リンパ腫（ATL）におけるゲノム情報と臨床情報を統合したリスクモデルを確立 --ATLの個別化医療を推進--. 京都大学プレスリリース. 2023-04-10.The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. To identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] 5.46, p < 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR 2.33, p = 0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATL-PI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3)

Diagnosis of biliary tract and ampullary carcinomas

Diagnostic methods for biliary tract carcinoma and the efficacy of these methods are discussed. Neither definite methods for early diagnosis nor specific markers are available in this disease. When this disease is suspected on the basis of clinical symptoms and risk factors, hemato-biochemical examination and abdominal ultrasonography are performed and, where appropriate, enhanced computed tomography (CT) and/or magnetic resonance cholangiopancreatography (MRCP) is carried out. Diagnoses of extrahepatic bile duct cancer and ampullary carcinoma are often made based on the presence of obstructive jaundice. Although rare, abdominal pain and pyrexia, as well as abnormal findings of the hepatobiliary system detected by hemato-biochemical examination, serve as a clue to making a diagnosis of these diseases. On the other hand, the early diagnosis of gallbladder cancer is scarcely possible on the basis of clinical symptoms, so when this cancer is found with the onset of abdominal pain and jaundice, it is already advanced at the time of detection, thus making a cure difficult. When gallbladder cancer is suspected, enhanced CT is carried out. Multidetector computed tomography (MDCT), in particular — one of the methods of enhanced CT — is useful for decision of surgical criteria, because MDCT shows findings such as localization and extension of the tumor, and the presence or absence of remote metastasis. Procedures such as magnetic resonance imaging, endoscopic ultrasonography, bile duct biopsy, and cholangioscopy should be carried out taking into account indications for these procedures in individual patients. However, direct biliary tract imaging is necessary for making a precise diagnosis of the horizontal extension of bile duct cancer

Pebbles and sand on asteroid (162173) Ryugu: In situ observation and particles returned to Earth

International audienceThe Hayabusa2 spacecraft investigated the C-type (carbonaceous) asteroid (162173) Ryugu. The mission performed two landing operations to collect samples of surface and subsurface material, the latter exposed by an artificial impact. We present images of the second touchdown site, finding that ejecta from the impact crater was present at the sample location. Surface pebbles at both landing sites show morphological variations ranging from rugged to smooth, similar to Ryugu’s boulders, and shapes from quasi-spherical to flattened. The samples were returned to Earth on 6 December 2020. We describe the morphology of >5 grams of returned pebbles and sand. Their diverse color, shape, and structure are consistent with the observed materials of Ryugu; we conclude that they are a representative sample of the asteroid