An Oligomeric Sulfated Hyaluronan and Silk-Elastinlike Polymer Combination Protects against Murine Radiation Induced Proctitis.
An Oligomeric Sulfated Hyaluronan and Silk-Elastinlike Polymer Combination Protects against Murine Radiation Induced Proctitis.
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DOI：
10.3390/pharmaceutics14010175
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发表时间：
2022-01-12
期刊：
影响因子：
5.4
通讯作者：
Ghandehari H
中科院分区：
文献类型：
--
作者：
Steinhauff D;Jensen MM;Griswold E;Jedrzkiewicz J;Cappello J;Oottamasathien S;Ghandehari H
半合成糖胺葡聚糖醚(SAGE)是一种短的、硫化的透明质酸，它结合了透明质酸的自然性质和化学硫化作用。在小鼠模型中，鼠尾草提供了对放射性直肠炎(RIP)的保护，RIP是下腹部放射治疗癌症的副作用。SAGE的抗炎作用已经在黏膜屏障部位的炎症性疾病中进行了研究；然而，很少有机制被发现，需要高通量的方法。将鼠尾草与类丝胶聚合物(SELP)结合，以促进小鼠的直肠蓄积。小鼠下腹部高剂量照射后，观察3天或直到达到人性化终点，然后评估行为疼痛反应和直肠炎症的组织学评估。对3天队列中的组织进行RNA测序，以确定SAGE-SELP的分子机制。3天后，接受鼠尾草-SELP组合的小鼠的疼痛反应显著降低，放射诱导的直肠炎症得到改善。接受药物-聚合物组合的小鼠比其他受辐射的小鼠存活时间长60%，其中一小部分显示出长期存活。测序揭示了Toll样受体、抗氧化活性、T细胞信号和与疼痛相关的通路的不同调节。这项研究阐明了SAGS的几个分子机制，并展示了预防RIP的有希望的措施。
Semisynthetic glycosaminoglycan ethers (SAGEs) are short, sulfated hyaluronans which combine the natural properties of hyaluronan with chemical sulfation. In a murine model, SAGEs provide protection against radiation induced proctitis (RIP), a side effect of lower abdominal radiotherapy for cancer. The anti-inflammatory effects of SAGE have been studied in inflammatory diseases at mucosal barrier sites; however, few mechanisms have been uncovered necessitating high throughput methods. SAGEs were combined with silk-elastinlike polymers (SELPs) to enhance rectal accumulation in mice. After high radiation exposure to the lower abdominal area, mice were followed for 3 days or until they met humane endpoints, before evaluation of behavioral pain responses and histological assessment of rectal inflammation. RNA sequencing was conducted on tissues from the 3-day cohort to determine molecular mechanisms of SAGE–SELP. After 3 days, mice receiving the SAGE–SELP combination yielded significantly lowered pain responses and amelioration of radiation-induced rectal inflammation. Mice receiving the drug–polymer combination survived 60% longer than other irradiated mice, with a fraction exhibiting long term survival. Sequencing reveals varied regulation of toll like receptors, antioxidant activities, T-cell signaling, and pathways associated with pain. This investigation elucidates several molecular mechanisms of SAGEs and exhibits promising measures for prevention of RIP.
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影响因子：
9.7
作者：
Kim, Chang Sup;Yang, Yun Jung;Cha, Hyung Joon
通讯作者：
Cha, Hyung Joon
DOI：
10.1016/j.ijrobp.2012.07.2373
发表时间：
2013-03-15
影响因子：
7
作者：
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14.9
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Ma'ayan A
影响因子：
11.2
作者：
Benitez A;Yates TJ;Lopez LE;Cerwinka WH;Bakkar A;Lokeshwar VB
通讯作者：
Lokeshwar VB
DOI：
10.1016/s0360-3016(00)00744-6
发表时间：
2000-11-01
影响因子：
7
作者：
Hovdenak, N;Fajardo, LF;Hauer-Jensen, M
通讯作者：
Hauer-Jensen, M