32970 research outputs found
Sort by
Discrete element numerical simulation of mechanical properties of methane hydrate-bearing specimen considering deposit angles
No full textMethane hydrate sediment (MHS) distributes under the seabed in different deposit angles according to the bottom simulating reflector (BSR) exhibitions. The mechanical properties of the combined sediment composed of soil and MHS dominate the stability of the slope. In this work, simulation models that consider the deposit angles, the confining pressures, loading velocities and hydrate saturation (Sh), were generated by using the discrete element method, following which the bi-axial compression of these models is simulated. The deformation response behavior of these models is studied systematically under different loading velocities, deposit angle, and hydrate saturation conditions. With increasing deposit angles, the peak strength approximately increased first and then decreased. The peak stress gradually decreases with increasing deposit angles when the hydrate saturation is more than 70% under the condition that the confining pressure is 10 MPa. The peak strength and stiffness of sediments increased with increasing Sh. The confining pressure enhanced the peak strength linearly, and the elastic modulus increased first and then decreased in a parabolic equation. Under different loading velocities conditions, the peak strength linearly increased, and the elastic modulus logarithmically increased with increasing loading velocity
Epstein-Barr Virus Exploits the Secretory Pathway to Release Virions
Full text linkHerpesvirus egress mechanisms are strongly associated with intracellular compartment remodeling processes. Previously, we and other groups have described that intracellular compartments derived from the Golgi apparatus are the maturation sites of Epstein-Barr virus (EBV) virions. However, the mechanism by which these virions are released from the host cell to the extracellular milieu is poorly understood. Here, I adapted two independent induction systems of the EBV lytic cycle in vitro, in the context of Rab GTPase silencing, to characterize the EBV release pathway. Immunofluorescence staining revealed that p350/220, the major EBV glycoprotein, partially co-localized with three Rab GTPases: Rab8a, Rab10, and Rab11a. Furthermore, the knockdown of these Rab GTPases promoted the intracellular accumulation of viral structural proteins by inhibiting its distribution to the plasma membrane. Finally, the knockdown of the Rab8a, Rab10, and Rab11a proteins suppressed the release of EBV infectious virions. Taken together, these findings support the hypothesis that mature EBV virions are released from infected cells to the extracellular milieu via the secretory pathway, as well as providing new insights into the EBV life cycle
エクソソーム随伴導入型薬物送達システムの開発
Full text linkRecently, mRNAs and microRNAs (miRNAs) have been identified in exosomes, which can be taken up by neighboring or distant cells. These exosomal-miRNAs may regulate gene expression in recipient cells. miRNAs are a type of non-coding RNA that induce post-transcriptional gene silencing of their target genes and regulate a wide range of biological processes, including apoptosis, differentiation, metabolism, and cell proliferation. According to recent reports, aberrant expression of miRNAs is associated with most pathological disease processes, including carcinogenesis. Therefore circulating onco-miRs are considered as significant therapeutic targets for cancer therapy. However, there is no report to regulate the function of miRNAs in exosomes. In this study, we developed novel drug delivery system using anti-exosome antibody-oligonucleotide conjugates (ExomiR-Tracker) for functional inhibition of circulating miRNAs. The “ExomiR-Tracker” is the world's first innovative molecule that has targeting property for exosome-recipient cells and specifically delivers nucleic acid medicines to the target cells. We found that ExomiR-Tracker can bind to the surface of exosomes and that the complexes are introduced into exosome-recipient cells then inhibit the activity of miRNA. We showed that ExomiR-Tracker can accumulate in cancerous tumors after intravenous administration. Existing technologies have difficulties for introducing anti-miR into exosomes and extremely low possibility to deliver anti-miR to exosome-recipient cells after intravenous administration. However, we successfully developed useful inhibition technology against exosomal-miRNA
異なる骨吸収抑制薬に起因する顎骨壊死様病変の早期段階における免疫病理的相違
No full textThere is limited information about denosumab-related osteonecrosis of the jaw (DRONJ), unlike bisphosphonate-related ONJ (BRONJ). The mode of action is clearly different between denosumab and bisphosphonates. DRONJ occurs mainly following tooth extraction in cancer patients treated with the combination of denosumab and other drugs including chemotherapy. However, DRONJ animal models similar to these clinical situations have not been developed. The aims of this study were to 1) create a new model of high-prevalence chemotherapy/anti-RANKL antibody-related ONJ-like lesions to mimic patients receiving a denosumab/chemotherapy combination; and 2) compare the histopathological and immunopathological findings in the early stages of BRONJ-like and anti-RANKL antibody-related ONJ-like lesions. Cyclophosphamide (CY) and anti-mouse RANKL monoclonal antibody (mAb) or zoledronate combination therapy (CY/mAb and CY/ZA, respectively) was performed to create ONJ-like lesions in female C57BL/6J mice. Both maxillary first molars were extracted at 3 weeks after drug administration. The animals were euthanized at either 2 or 4 weeks after tooth extraction. Increased necrotic bone and empty lacunae with decreased living bone and osteocyte numbers were common histopathological findings in CY/mAb- and CY/ZA-induced impaired wound healing at 4 weeks after tooth extraction, and they were diagnosed as ONJ-like lesions based on validation of BRONJ and DRONJ in humans. In areas of impaired healing at 2 weeks post-extraction, decreases in angiogenesis and F4/80+LYVE-1− macrophages were noted as common immunopathological findings, although anti-angiogenesis was worse with CY/mAb than with CY/ZA. Interestingly, CY/mAb did not reduce F4/80+LYVE-1+ cells and normal lymphangiogenesis remained, whereas CY/ZA profoundly suppressed the larger size of F4/80+LYVE-1+ cells, similar to vessels with a concomitant decrease in lymphangiogenesis. Therefore, the distribution of the larger size of F4/80+LYVE-1+ cells differed in the early stages between different antiresorptive-induced ONJ-like lesions in conjunction with lymphangiogenesis, although the histopathological findings were similar. These findings suggest that the pathogenesis of BRONJ and DRONJ may differ due to the distributions of F4/80+LYVE-1+ tube-like-structured cells.長崎大学学位論文 学位記番号:博(医歯薬)甲第1259号 学位授与年月日:令和2年6月3日Author: Hiroki Hayano, Shinichiro Kuroshima, Muneteru Sasaki, Saki Tamaki, Maaya Inoue, Akira Ishisaki, Takashi SawaseCitation: Bone, 135, 115308; 202
非小細胞肺癌に対する肺切除術後の運動耐容能に影響を及ぼす要因
No full textPurpose: We investigated, in patients who underwent lung resection for non–small cell lung cancer (NSCLC), the magnitude of early limitation in functional exercise capacity and the associations with pre- and postoperative factors. Methods: Consecutive patients with preoperative clinical stage I to IIIA NSCLC who underwent lung resection were prospectively enrolled. We measured functional exercise capacity (6-minute walk distance [6MWD]) and skeletal muscle strength (handgrip [HF] and quadriceps force [QF]) within 2 days prior to surgery and on day 7 postoperatively. Results: Two hundred eighteen participants were recruited (median age 69 years) of whom 49 developed postoperative complications (POCs). 6MWD was markedly decreased (514 m vs 469 m, P < .001); HF and QF were slightly decreased following surgery. Multiple linear regression showed that preoperative vital capacity (P < .01), QF (P < .05), the duration of chest tube drainage (P < .001), and presence of POCs (P < .05) were significant predictors. However, intraoperative factors were not significantly associated with the decline in 6MWD. Conclusions: These results suggest that patients with preoperative impairments in pulmonary function and muscle strength, and those who require prolonged chest tube drainage or develop POCs are likely to have impaired exercise capacity. Therefore, individual assessment and follow-up of patients with such factors is indicated.長崎大学学位論文 学位記番号:博(医歯薬)甲第1260号 学位授与年月日:令和2年6月3日Author: Masato Oikawa, Masatoshi Hanada, Hiroki Nagura, Tomoshi Tsuchiya, Keitaro Matsumoto, Takuro Miyazaki, Terumitsu Sawai, Naoya Yamasaki, Takeshi Nagayasu, Ryo KozuCitation: Integrative Cancer Therapies, 19, 1534735420923389; 202
Frequent unregulated use of antibiotics in rural Cambodian infants
Full text linkBACKGROUND: Despite a high prevalence of antibiotic resistance in Cambodia, few studies have assessed health-seeking behaviour and the use of antibiotics by caregivers of young children in Cambodia. METHODS: We conducted a cross-sectional survey of infants <12 months of age and their caregivers, assessing the frequency of reported illness, common symptoms and associated health-seeking behaviour through structured questionnaires administered by trained fieldworkers at a home visit. In a subset of these participants, ages 4-8 months with no acute malnutrition, we conducted a 3-month surveillance with fortnightly home visits. RESULTS: Of 149 infants (ages 1-11 months, 54.4% male) enrolled in the cross-sectional study, 76 (51.4%) reported symptoms of diarrhoea, fever or cough in the previous 14 d, with associated use of antibiotics reported in 22 (14.8%) infants. In 47 infants enrolled in the longitudinal surveillance, there were 141 reported episodes of illness in 44 (94%) infants with 21 infants (45%) reported to have received antibiotics in 32/141 (22.7%) episodes. Amoxicillin was the most commonly reported antibiotic in both surveys (68% [40/59 episodes reporting the use of antibiotics]). CONCLUSIONS: Antibiotic usage is high in this population and appears to be occurring largely outside of the formal healthcare system
左半側空間無視患者に対するプリズム順応が聴覚の空間性注意に与える影響：非ランダム化比較試験
Full text link長崎大学学位論文 [学位記番号]博（医歯薬）甲第1262号 [学位授与年月日]令和2年6月3
Erosion of CAD/CAM restorative materials and human enamel: An in situ/in vivo study
No full textThis in situ/in vivo study aimed to evaluate the effects of erosion on the surface microhardness, substance loss, and surface roughness of CAD/CAM restorative materials and human enamel. This study used a 2-treatment (14 days each) crossover design with 8 healthy volunteers. Each volunteer wore an intraoral appliance containing 3 CAD/CAM restorative material specimens [IPS e.max CAD, Lava Ultimate CAD/CAM Restorative, and a poly (methyl methacrylate) (PMMA) block for CAD/CAM] and 1 human enamel specimen. The specimens were subjected to in vivo erosion cycles by rinsing with 150 ml of cola drink (4 × 5 min/day) for 14 days. The surface microhardness, substance loss, and surface roughness of the specimens were measured at baseline (T1), day 7 (T2) and day 14 (T3). The data were statistically analyzed using repeated measures ANOVA and Tukey's test (α = 0.05). After erosion, significant increases in substance loss and surface roughness were observed for enamel, though the surface roughness and substance profile of the tested restorative materials remained unchanged. Erosion significantly decreased the surface microhardness of all materials. For IPS e.max and Lava Ultimate, a significantly higher percentage of surface microhardness loss (%SMHl) was found at T3 than at T2, while no significant difference was found between T2 and T3 for enamel and the PMMA block. In conclusion, CAD/CAM restorative materials showed smaller changes in surface roughness and the surface profile than human enamel after in situ/in vivo erosion. However, CAD/CAM restorative materials and human enamel showed similar changes in surface microhardness after in situ/in vivo erosion
Recent Strategies for Targeted Brain Drug Delivery
Full text linkBecause the brain is the most important human organ, many brain disorders can cause severe symptoms. For example, glioma, one type of brain tumor, is progressive and lethal, while neurodegenerative diseases cause severe disability. Nevertheless, medical treatment for brain diseases remains unsatisfactory, and therefore innovative therapies are desired. However, the development of therapies to treat some cerebral diseases is difficult because the blood-brain barrier (BBB) or blood-brain tumor barrier prevents drugs from entering the brain. Hence, drug delivery system (DDS) strategies are required to deliver therapeutic agents to the brain. Recently, brain-targeted DDS have been developed, which increases the quality of therapy for cerebral disorders. This review gives an overview of recent brain-targeting DDS strategies. First, it describes strategies to cross the BBB. This includes BBB-crossing ligand modification or temporal BBB permeabilization. Strategies to avoid the BBB using local administration are also summarized. Intrabrain drug distribution is a crucial factor that directly determines the therapeutic effect, and thus it is important to evaluate drug distribution using optimal methods. We introduce some methods for evaluating drug distribution in the brain. Finally, applications of brain-targeted DDS for the treatment of brain tumors, Alzheimer's disease, Parkinson's disease, and stroke are explained