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131.
Masatoshi Murayama Hirohito Hirata Makoto Shiraki Juan L. Iovanna Takayoshi Yamaza Toshio Kukita Toshihisa Komori Takeshi Moriishi Masaya Ueno Tadatsugu Morimoto Masaaki Mawatari Akiko Kukita 《Journal of cellular physiology》2023,238(3):566-581
Nuclear protein 1 (NUPR1) is a stress-induced protein activated by various stresses, such as inflammation and oxidative stress. We previously reported that Nupr1 deficiency increased bone volume by enhancing bone formation in 11-week-old mice. Analysis of differentially expressed genes between wild-type (WT) and Nupr1-knockout (Nupr1-KO) osteocytes revealed that high temperature requirement A 1 (HTRA1), a serine protease implicated in osteogenesis and transforming growth factor-β signaling was markedly downregulated in Nupr1-KO osteocytes. Nupr1 deficiency also markedly reduced HtrA1 expression, but enhanced SMAD1 signaling in in vitro-cultured primary osteoblasts. In contrast, Nupr1 overexpression enhanced HtrA1 expression in osteoblasts, suggesting that Nupr1 regulates HtrA1 expression, thereby suppressing osteoblastogenesis. Since HtrA1 is also involved in cellular senescence and age-related diseases, we analyzed aging-related bone loss in Nupr1-KO mice. Significant spine trabecular bone loss was noted in WT male and female mice during 6−19 months of age, whereas aging-related trabecular bone loss was attenuated, especially in Nupr1-KO male mice. Moreover, cellular senescence-related markers were upregulated in the osteocytes of 6−19-month-old WT male mice but markedly downregulated in the osteocytes of 19-month-old Nupr1-KO male mice. Oxidative stress-induced cellular senescence stimulated Nupr1 and HtrA1 expression in in vitro-cultured primary osteoblasts, and Nupr1 overexpression enhanced p16ink4a expression in osteoblasts. Finally, NUPR1 expression in osteocytes isolated from the bones of patients with osteoarthritis was correlated with age. Collectively, these results indicate that Nupr1 regulates HtrA1-mediated osteoblast differentiation and senescence. Our findings unveil a novel Nupr1/HtrA1 axis, which may play pivotal roles in bone formation and age-related bone loss. 相似文献
132.
Rosalina Lara-Rico Claudia M. López-Badillo Jesús A. Claudio-Rizo Denis. A. Cabrera-Munguía Juan J. Becerra-Rodríguez Roberto Espinosa-Neira Brenda R. Cruz-Ortiz 《Biopolymers》2023,114(6):e23538
In this work, hydrogels based on semi-interpenetrating polymeric networks (semi-IPN) based on collagen-polyurethane-alginate were studied physicochemically and from different approaches for biomedical application. It was determined that the matrices in the hydrogel state are crosslinked by the formation of urea and amide bonds between the biopolymer chains and the polyurethane crosslinker. The increment in alginate content (0–40 wt%) significantly increases the swelling capacity, generating semi-crystalline granular structures with improved storage modulus and resistance to thermal, hydrolytic, and proteolytic degradation. The in vitro bioactivity results indicated that the composition of these novel hydrogels stimulates the metabolic activity of monocytes and fibroblasts, benefiting their proliferation; while in cancer cell lines, it was determined that the composition of these biomaterials decreases the metabolic activity of breast cancer cells after 48 h of stimulation, and for colon cancer cells their metabolic activity decreases after 72 h of contact for the hydrogel with 40 wt% alginate. The matrices show a behavior of multidose release of ketorolac, and a higher concentration of analgesic is released in the semi-IPN matrix. The inhibition capacity of Escherichia coli is higher if the polysaccharide concentration is low (10 wt%). The in vitro wound closure test (scratch test) results indicate that the hydrogel with 20 wt% alginate shows an improvement in wound closure at 15 days of contact. Finally, the bioactivity of mineralization was evaluated to demonstrate that these hydrogels can induce the formation of carbonated apatite on their surface. The engineered hydrogels show biomedical multifunctionality and they could be applied in soft and hard tissue healing strategies, anticancer therapies, and drug release devices. 相似文献
133.
Leandro Fainburg David Sabadin Juan Martín Díaz de Astarloa Pedro Fernández Iriarte 《Journal of fish biology》2023,102(2):455-464
The mud flounder Paralichthys orbignyanus (Pleuronectiformes, Paralichthyidae) inhabits shallow waters of low salinities and mud bottoms in the temperate marine coastal regions of the Bonaerensean Ecoregion of the Argentinean Biogeographic Province in the south-western Atlantic Ocean. Specimens of P. orbignyanus were collected from Lagoa dos Patos (LDP) (southern Brazil), Mar Chiquita (MCH) and Marisol (MAR) both located in Buenos Aires (Argentina), and San Antonio Oeste (SAO) in the San Matías Gulf, Rio Negro (Argentina). A fragment of the mitochondrial DNA of the Control Region and seven microsatellite loci were characterized. In the Control Region, P. orbignyanus showed high variability, low nucleotide diversity, mild population expansion and a coalescence time of 35,000 years before the present. Flounders provided evidence of a genetic structure between the sampling sites LDP, MCH, MAR vs. SAO. On the other hand, P. orbignyanus displayed a lower to moderate contemporary genetic structure among all samples except between LDP and MCH. With no evidence of isolation by distance, this analysis supports a model of limited gene flow that is likely to be associated with a consistent larvae retention in all sampling sites. In addition, the present connectivity is ascribed to a lower migration process from SAO in the San Matías Gulf congruent with the prevailing littoral drift. 相似文献
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135.
Andrea Evangelina Arcángel Emiliano Alexis Rodríguez Juan Francisco Saad Paula de la Barra Maite Andrea Narvarte Lorena Pía Storero Patricio Javier Pereyra 《Journal of phycology》2023,59(6):1310-1322
Population dynamics can be influenced by physical and biological factors, particularly in stressful environments. Introduced species usually have great physiological plasticity, resulting in populations with different traits. Undaria pinnatifida, a macroalga originally described from northeast Asia, was introduced in Northern Patagonia, Argentina (San Matías Gulf) around 2010. To describe the spatio-temporal variability in population structure and morphometry of U. pinnatifida, we conducted monthly field samplings for 2 years at the intertidal area of two contrasting sites in the San Matías Gulf. Individuals of U. pinnatifida were classified by developmental stage, and their morpho-gravimetric variables were measured. In both intertidal sites juveniles were found in higher proportion during austral autumn and grew and matured during the autumn-winter months (from May onwards), and individuals senesced during early austral summer (December and January). Conversely, density and biomass were largely different between sites, and individuals showed slight morphological variability between sites. Environmental (e.g., nutrient concentration, available substrate) and biological factors (e.g., facilitation, competition) may explain the observed differences. Since there is not a macroalga with U. pinnatifida morphometrical characteristics in the intertidal environments of San Matías Gulf, studying this recent introduction gives us a better understanding of its potential ecological effects. 相似文献
136.
【背景】由于抗生素的滥用,使得细菌耐药性问题严峻,寻找解决耐药性细菌感染的治疗策略迫在眉睫。临床上,中药与抗菌药物联用在抗耐药性细菌感染方面效果显著。【目的】研究香芹酚联合头孢曲松对耐药性沙门氏菌(SJ2)的协同效应及机制。【方法】通过二倍肉汤稀释法测定香芹酚和头孢曲松对SJ2的最小抑菌浓度(minimal inhibitory concentration, MIC);通过棋盘法和生长曲线测定探究香芹酚和头孢曲松联合抗SJ2活性;通过膜电位检测、胞外碱性磷酸酶(alkaline phosphatase, AKP)含量测定、菌体内抗生素蓄积分析、细菌生存活力测定及扫描电镜研究香芹酚联合头孢曲松对SJ2细胞壁、细胞膜的影响。【结果】香芹酚和头孢曲松对SJ2的MIC分别为256μg/mL和2 048μg/mL;香芹酚联合头孢曲松对SJ2具有协同作用,其分级抑制浓度指数(fractional inhibitory concentration index, FICI)为0.375;香芹酚可协同头孢曲松使SJ2细胞膜出现去极化,显著增加AKP泄漏至胞外的量(P<0.05),显著增加菌体胞内抗... 相似文献
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139.
Brasilicardin A (BraA)是从致病性放线菌巴西诺卡菌(Nocardia brasiliensis) IFM 0406中发现的具有显著免疫抑制作用(IC50=0.057μg/mL)的二萜糖苷类化合物。BraA发挥免疫抑制活性的作用机制与现有临床常用的免疫抑制剂不同,BraA通过抑制氨基酸转运体L系统的转运进而影响T-淋巴细胞对氨基酸的摄入而发挥免疫抑制作用。相比目前已知的免疫抑制剂环孢菌素A、子囊霉素和他克莫司等,BraA在小鼠混合淋巴细胞反应中显示低毒、高效的优势。因此,BraA作为新型的免疫抑制剂,极具开发潜力,已成为全球免疫抑制剂发现新领域。但其结构复杂、合成困难,原菌种产率低且具有致病性,BraA及其类似物的获得已成为此类新型免疫抑制剂研究的瓶颈。本文综述了BraA的分子特征、药理活性、作用机制、目前获得的BraA类似物和衍生化方面的研究进展,以期为BraA及其类似物的高效生产提供参考。 相似文献
140.
Xanthocillin具有显著的抗菌活性,结构中含有独特的异腈基。本文通过对蛇足石杉(Huperzia serrata)内生真菌产黄青霉菌(Penicillium chrysogenum)MT-40基因组的测序分析,利用本地BLAST等生物信息学分析工具挖掘具有合成xanthocillin类似物潜力的基因簇,结合米曲霉(Aspergillus oryzae)NSAR1异源表达技术实现基因簇中关键基因的功能鉴定。结果成功从内生真菌P.chrysogenum MT-40中发现一个合成xanthocillin类似物的生物合成基因簇(命名为for),for基因簇中的关键生物合成基因forB编码的异腈基合成酶可以催化合成2-formamido-3-(4-hydroxyphenyl)acrylic acid,基因forG编码的P450酶可以催化2-formamido-3-(4-hydroxyphenyl)acrylic acid的二聚化生成xanthocillin类似物N,N′-(1,4-bis(4-hydroxyphenyl)buta-1,3-diene-2,3-diyl)diformamide。本文研究结果为进一步从真菌中发现xanthocillin类似物提供参考。 相似文献