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21.
Samuel Cibulski Thais Fumaco Teixeira Ana Paula Muterle Varela Matheus Fabião de Lima Gabriela Casanova Yuri Mangueira Nascimento Josean Fechine Tavares Marcelo Sobral da Silva Patrícia Sesterheim Diogo Onofre Souza Paulo Michel Roehe Fernando Silveira 《Vaccine》2021,39(3):571-579
Vaccine adjuvants are compounds that enhance/prolong the immune response to a co-administered antigen. Saponins have been widely used as adjuvants for many years in several vaccines – especially for intracellular pathogens – including the recent and somewhat revolutionary malaria and shingles vaccines. In view of the immunoadjuvant potential of Q. brasiliensis saponins, the present study aimed to characterize the QB-80 saponin-rich fraction and a nanoadjuvant prepared with QB-80 and lipids (IMXQB-80). In addition, the performance of such adjuvants was examined in experimental inactivated vaccines against Zika virus (ZIKV). Analysis of QB-80 by DI-ESI-ToF by negative ion electrospray revealed over 29 saponins that could be assigned to known structures existing in their congener Q. saponaria, including the well-studied QS-21 and QS-7. The QB-80 saponins were a micrOTOF able to self-assembly with lipids in ISCOM-like nanoparticles with diameters of approximately 43 nm, here named IMXQB-80. Toxicity assays revealed that QB-80 saponins did present some haemolytical and cytotoxic potentials; however, these were abrogated in IMXQB-80 nanoparticles. Regarding the adjuvant activity, QB-80 and IMXQB-80 significantly enhanced serum levels of anti-Zika virus IgG and subtypes (IgG1, IgG2b, IgG2c) as well as neutralized antibodies when compared to an unadjuvanted vaccine. Furthermore, the nanoadjuvant IMXQB-80 was as effective as QB-80 in stimulating immune responses, yet requiring fourfold less saponins to induce the equivalent stimuli, and with less toxicity. These findings reveal that the saponin fraction QB-80, and particularly the IMXQB-80 nanoadjuvant, are safe and capable of potentializing immune responses when used as adjuvants in experimental ZIKV vaccines. 相似文献
22.
Tomomi Yamaguchi Shujiro Hayashi Daisuke Hayashi Takeshi Matsuyama Norimichi Koitabashi Kenichi Ogiwara Masaaki Noda Chiai Nakada Shinya Fujiki Akira Furutachi Yasuhiko Tanabe Michiko Yamanaka Aki Ishikawa Miyako Mizukami Asako Mizuguchi Kazumitsu Sugiura Makoto Sumi Hirokuni Yamazawa Atsushi Izawa Yuko Wada Tomomi Fujikawa Yuri Takiguchi Keiko Wakui Kyoko Takano Shin-Ya Nishio Tomoki Kosho 《American journal of medical genetics. Part A》2023,191(1):37-51
Vascular Ehlers–Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification-based next-generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys–Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non-Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in-frame deletions, and one (2.9%) had a multi-exon deletion, including two deceased patients analyzed with formalin-fixed and paraffin-embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples. 相似文献
23.
This review describes the historical development of aesthetic surgery in Japan and parallels with the development of the
specialty in the United States. The focus is on the consequences of aesthetic surgery in the male patient when collaboration
between mental health clinicians and surgeons lags. The cultural, social, and psychological issues raised are relevant to
the diverse cultural groups now seeking aesthetic surgery in the United States. Case illustrations are a reminder to aesthetic
surgeons of the potential need for more comprehensive evaluation in the group of male patients who may be at added risk for
negative outcomes in terms of satisfaction. 相似文献
24.
Homotypic Adhesion through Carcinoembryonic Antigen Plays a Role in Hepatic Metastasis Development 总被引:2,自引:0,他引:2
Toshiaki Yoshioka Takashi Masuko Hitoshi Kotanagi Osamu Aizawa Yuri Saito Hiroshi Nakazato Kenji Koyama Yoshiyuki Hashimoto 《Cancer science》1998,89(2):177-185
We established a cell line with high metastatic potential to the liver (LS-LM4) after four successive repetitions of splenic injection of liver-metastatic cells in SCID mice. This cell line strongly expressed CEA and showed increased homotypic adhesion as compared with the parent cell line (LS174T). To examine the role of CEA in the increased homotypic adhesion, LS-LM4 cells were treated with anti-CEA antibody and subjected to an in vitro adhesion and aggregation assay. Further, to study the role of CEA in the hepatic metastasis of cells with high metastatic potential, LS-LM4 cells were treated with anti-CEA antibody, and the inhibition of hepatic metastasis after splenic injection in vivo was examined. There was a 62% decrease in the homotypic adhesion of anti-CEA antibody-treated (100 μg/ml) LS-LM4 cells under a Ca2+ -free condition as compared with the control ( P <0.01). Anti-CEA antibody (100 μg/ml) inhibited cell aggregation under a Ca2+ -free condition ( P <0.05). Treatment with anti-E-cadherin antibody (60 μ/ml) plus anti-CEA antibody (100 μg/ml) inhibited cell aggregation more potently than anti-E-cadherin antibody treatment alone in the presence of Ca2+ . In vivo , there was a 75% decrease in the number of hepatic metastatic nodules in the G125 anti-CEA antibody-treated group as compared with the control group ( P <0.01). Similarly, there was a 40% decrease in the diameter of metastatic nodules and there was a 90% decrease in total tumor volume of hepatic metastasis in the G125 anti-CEA antibody-treated group as compared with the control ( P <0.01). These results suggest that increased metastatic potential to the liver is at least partly due to increased homotypic binding mediated by CEA. 相似文献
25.
Yuri Takahashi Yasuo Miyoshi Chie Takahata Natsumi Irahara Tetsuya Taguchi Yasuhiro Tamaki Shinzaburo Noguchi 《Clinical cancer research》2005,11(4):1380-1385
PURPOSE: LATS1 and LATS2 are tumor suppressor genes implicated in the regulation of cell cycle. Methylation status of the promoter regions of these genes as well as its correlation with their mRNA levels were studied in human breast cancers. Correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics of breast tumors were also studied. EXPERIMENTAL DESIGN: Methylation status of promoter regions of LATS1 and LATS2 was studied by a methylation-specific PCR and mRNA expression levels of LATS1 and LATS2 were determined by a real-time PCR assay in 30 breast cancers. In addition, correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics was studied in 117 breast cancers. RESULTS: Methylation-specific PCR showed that of 30 tumors, LATS1 promoter region was hypermethylated in 17 tumors (56.7%) and LATS2 promoter region was hypermethylated in 15 (50.0%) tumors. LATS1 mRNA levels in breast tumors with hypermethylation (2.15 +/- 0.37, mean +/- SE) were significantly (P < 0.01) lower than those without hypermethylation (6.09 +/- 1.38), and LATS2 mRNA levels in breast tumors with hypermethylation (1.42 +/- 0.66) were also significantly (P < 0.01) lower than those without hypermethylation (3.10 +/- 1.00). The decreased expression of LATS1 or LATS2 mRNA was significantly associated with a large tumor size, high lymph node metastasis, and estrogen receptor and progesterone receptor negativity. Furthermore, the decreased expression of LATS1 mRNA, but not LATS2 mRNA, was significantly (P < 0.05) associated with a poor prognosis. CONCLUSIONS: Hypermethylation of the promoter regions of LATS1 and LATS2 likely plays an important role in the down-regulation of their mRNA levels in breast cancers, and breast cancers with a decreased expression of LATS1 or LATS2 mRNA levels have a biologically aggressive phenotype. 相似文献
26.
Alexey V. Osipov Vladislav G. Starkov Elena V. Ryumina Leonid V. Kozlov Yvon Doljansky Yuri N. Utkin 《Toxicon》2005,46(4):394-403
Two forms of complement-depleting cobra venom factor (CVFm1 and CVFm2), possessing molecular masses of 142.6 kDa (CVFm1) and 143.1 kDa (CVFm2), according to MALDI mass-spectrometry, were isolated from the Naja melanoleuca cobra venom. As shown by polyacrylamide gel electrophoresis in the presence of SDS, both forms similarly to factor from the Naja kaouthia cobra venom (CVFk) consist of three polypeptide chains with molecular masses of about 70, 50, and 30 kDa, the two large subunits being glycosylated. As determined by MALDI mass-spectrometry, 30 kDa subunits of CVFm1 and CVFm2 have considerably different finger-prints of tryptic digests that suggests differences in their amino acid sequences. A study of activity in vivo has shown no significant differences in C3 consumption by CVFm1, CVFm2 and CVFk in mouse blood. However, as shown by an immunoassay method, they differ in their ability to activate the complement system via C3 conversion, the ratio of these activities for CVFm1:CVFm2:CVFk being 2.5:1.6:1. Kinetic studies using a hemolytic test showed that complement depletion by CVFm1 is faster than that by CVFm2. Thus, for the first time the presence in a single venom of two forms of CVF differing by both amino acid sequence and biological activity has been shown. 相似文献
27.
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29.
The theoretical stress-strain model for compressed composite cement materials’ behavior without empirical coefficients was proposed by Iskhakov in 2018. This model includes the following main parameters describing concrete behavior: stresses and strains corresponding to the border between the elastic and non-elastic behavior stages of a concrete specimen, ultimate elastic strains, and stresses and strains at the end of the post-peak region. Particular attention is focused on the descending branch of the stress-strain diagram, as well as on the analysis of concrete elastic and plastic potentials. These potentials are important for assessing the dynamic response of the concrete element section, as well as for concrete creep analysis. The present research is aimed at experimental verification of the above-mentioned theoretical model. The obtained experimental results are in good agreement with the theoretical ones, which confirms the model’s accuracy and enables a significant reduction in the empirical coefficients number in compressed reinforced concrete elements design. This, in turn, represents the scientific novelty of this study. 相似文献
30.
PurposeTo compare the diagnosis and treatment outcome of lacrimal drainage obstruction of patients who underwent systemic chemotherapy (CTx) or radioactive iodine treatment (RAI) by using dacryoendoscopy and at the same time performing dacryoendoscopy-guided silicone tube insertion (STI) to treat epiphora.MethodsFrom July 2017 to December 2020, the medical records of 11 patients (16 eyes) were diagnosed with lacrimal drainage obstruction after CTx or RAI and underwent dacryoendoscopy-guided STI were reviewed retrospectively. We tried to count the number of obstructive sites in total patients using slit-lamp examination and dacryoendoscopic findings.ResultsA total of 11 patients, 16 eyes, were enrolled in this study. The onset of epiphora in the CTx group (3.0 ± 4.0 months) was significantly shorter than that in the RAI group (52.6 ± 36.5 months, p = 0.001). There were total 32 obstructive sites including 28 obstructive sites of dacryoendoscopic findings and four sites of punctual stenosis in total 16 cases. Using dacryoendoscopy, granulation findings was dominant in RAI patients (p = 0.038) and mucus finding was frequent mostly in lacrimal sac and canaliculus. In the CTx group, mucosal edema finding was dominant (p = 0.038) and fibrotic membrane finding was frequent in all levels of lacrimal drainage system. Regarding the obstructive location, lacrimal sac was the most frequently obstructed site in the two groups (p = 0.038).ConclusionsThe onset of epiphora in the CTx group was significantly earlier than in the RAI group. In the CTx group, mucosal edema finding was frequent in all levels of lacrimal drainage system. In the RAI group, granulation finding was frequent mostly in lacrimal sac and canaliculus. Since the clinical outcome was satisfactory, intervention with dacryoendoscopy-guided STI could be a treatment of choice in patients with epiphora after CTx or RAI. 相似文献