作者: Song, Huichen ; Jiang, Yufei ; Ding, Jiaqi ; Cao, Mingxi ; Jiang, Xiaohong ; Yin, Xiaojiao ; Wang, Jin ; Chen, Silin ; Li, Botao ; Li, Liang ; Wang, Chen ; Li, Jing ; Chen, Jiangning ; Zhou, Zhen ; Jiang, Wantong ; Zhang, Yujing ; Liu, Jiachen ; Li, Weili ; Li, Jiaxin ; Shi, Huanhuan

Inflammatory bowel disease (IBD) is a group of chronic relapsing diseases associated with inflammatory disorders and microbial dysbiosis of the intestine. The use of traditional Chinese medicine (TCM) to treat colitis has the advantage of fewer side effects, but the molecular mechanism is not clear. Recently, miRNAs have been recognized as novel functional small molecules in plants that have regulatory effects on biological activities. This study mainly investigated the mechanism of action of MIR2911 from Honeysuckle, the main component of TCM preparations for colitis. The results demonstrated that MIR2911 can be absorbed through the diet and secreted within host small extracellular vesicles (sEVs), acting directly on intestinal bacteria, reducing the abundance of Escherichia-Shigella, and improving colitis symptoms. This study provides a new theoretical basis for the molecular mechanism of TCM therapy and identifies a potential new drug a new drug target for the treatment of colitis.

2024-06-01·Zhonghua nan ke xue = National journal of andrology

[Lycium barbarum miR2911-loaded exosomes promote spermatogenic function recovery in rats with non-obstructive azoospermia by regulating Wnt/β-catenin signaling pathways].

Article

作者: Tian, Jia ; Ma, Liang-Hong ; Xie, Zhi-Yuan ; Song, Ai-Hua ; Zhou, Yue ; Pei, Cheng-Bin

OBJECTIVE:

To investigate the effect of exosomes loaded with Lycium barbarum miRNA (Lb-miR2911) on spermatogenic function recovery in non-obstructive azoospermia (NOA) rats through cross-regulation of the Wnt/β-catenin signaling pathways.

METHODS:

We established an NOA model in 30 four-week-old male SD rats by intraperitoneal injection of busulfan. At 5 weeks after modeling, we equally randomized the rats into a model control group (MC，untreated), an Lb-miR2911EXO group (Lb-miR2911EXO ，treated by intratesticular injection of Lb-miR2911-loaded exosomes), and a sham group (Shame，treated by intratesticular injection of exosomes-empty drug), with another 10 male SD rats taken as normal controls（NC）. We observed the uptake and metabolic changes of Lb-miR2911 in the testis tissue of the rats by RNA FISH at 2 and 6 weeks after treatment, detected cell proliferation, spermatogenesis and gene expressions of the Wnt/β-catenin signaling pathways in the testis tissue by Transcriptome sequencing analysis combined with Western blot and RT-PCR at 12 weeks, evaluated the recovery of the spermatogenic function based on the testis tissue morphology and sperm quality, and assessed the organ toxicity of Lb-miR2911 in the tissue and organs of the rats based on histomorphological analysis and the levels of serum TNF-α, IL-1β, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and other relevant indicators.

RESULTS:

After 12 weeks of treatment, histomorphological analysis showed regular arrangement of spermatogenic cells at all levels in the testis tissue, with a large number of mature sperm in the tubular lumen, and with significantly higher Johnsen scores, testis weight, testicular index, sperm concentration and sperm motility in the Lb-miR2911EXO than in the sham group (all P< 0.05). Compared with the model controls, the Lb-miR2911EXO group exhibited remarkably down-regulated gene expression of DACT3 (P< 0.05), up-regulated expressions of DVL2 and β-catenin (P< 0.05), elevated levels of p-DVL2 and β-catenin (nucleus) proteins (P< 0.05), increased expressions of cell proliferation-related genes CCND1, CCNE1 and CCNE2 (P< 0.05) and spermatogenesis-related genes DMC1, CCR6, JAM2 and KLC3 (P< 0.05). No pathological changes were observed in the lung, liver and kidney tissues of the rats, or in the levels of serum TNF-α, IL-1β, AST, ALT, creatinine and urea nitrogen in the rats treated with Lb-miR2911EXO compared with the normal controls (P > 0.05).

CONCLUSION:

Lb-miR2911-loaded exosomes promote spermatogenic function recovery in NOA rats through cross-regulation of the DACT3, Wnt and β-catenin signaling pathways.

2024-03-06·Journal of agricultural and food chemistry

Atypical Plant miRNA cal-miR2911: Robust Stability against Food Digestion and Specific Promoting Effect on Bifidobacterium in Mice

Article

作者: Li, Yinglei ; Xu, Qin ; Wang, Jianing ; Wang, Xingyu ; Qin, Xinshu ; Yang, Xingbin ; Xu, Ke ; Li, Ying ; Xin, Yirao ; Zhang, Yi

Previous studies showed that cal-miR2911, featuring an atypical biogenesis, could target genes of virus and in turn inhibit virus replication. Given its especial sequence motif and cross-kingdom potential, the stability of miR2911 under digestive environment and its impact on intestinal microbes in mice were examined. The results showed that miR2911 was of considerable stability during oral, gastric, and intestinal digestion. The coingested food matrix enhanced its stability in the gastric phase, contributing to the existence of miR2911 in mouse intestines. The survival miR2911 promoted the growth of Bifidobacterium in mice and maintained the overall composition and diversity of the gut microbiota. miR2911 specifically entered the cells of Bifidobacterium adolescentis and potentially modulated the gene expression as evidenced by the dual-luciferase assay. The current study provided evidence on the cross-kingdom communication between dietary miRNAs and gut microbes, suggesting that modulating target bacteria using miRNAs for nutritional and therapeutic ends is promising.

项与 MIR2911 相关的新闻（医药）

2022-07-12

·BioBAY

精英周丨2022年金鸡湖科学家论坛设：核酸药物开发论坛

苏州国际精英创业周是苏州重点打造的重大招才引智活动，2009年起已连续举办十三届，2021年，苏州工业园区在精英创业周期间重磅推出金鸡湖科学家论坛，旨在聚集新兴产业和前沿技术领域的顶尖科学家，打造前沿基础研究与技术工程研究、产品开发创新的深度互动平台。7月11日，2022年第十四届苏州国际精英创业周园区分会场在金鸡湖国际会议中心顺利举办。2022年金鸡湖科学家论坛设五大生物医药创新主题论坛——细胞治疗论坛、核酸药物开发论坛、新型抗体药物开发论坛、Biotech前沿技术论坛以及创新医疗器械论坛暨医工融合创新发展高峰论坛。论坛邀请众多学术界与产业界一线一流专家，就生物医药前沿技术最新研究成果与转化应用展开报告，促进中国生物医药的创新发展。论坛二：核酸药物开发论坛嘉宾合影领导致辞园区人大工委副主任孙燕燕表示：园区已在国家级经开区综合考评中实现六连冠，跻身科技部建设世界一流高科技园区序列，获批建设“国家生物药技术创新中心、第三代半导体技术创新中心、新一代人工智能创新发展试验区”，拥有科技企业超万家，各类人才总数连续多年保持全国开发区第一。嘉宾观点靶向RNA世界赛诺菲中国研究负责人中国研究院院长肖昌春表示：RNA在不同细胞、甚至胞内/胞外结构不尽相同，这种特异性使得RNA在特定的细胞中有特定的结构。但是部分RNA仍然存在刚性二级/三级结构，为未来的小核酸药物设计提供了基础。miRNA具有调控能力，可与靶mRNA特异性结合，引起靶mRNA的降解和抑制其反应，在基因治疗领域具有应用潜力。可以期待，未来5-10年，RNA技术将会变得成熟。广谱抗病毒核酸药：MIR2911南京大学生物化学教授、生命科学学院院长张辰宇表示：中药金银花中，MIR291稳定高浓度地存在于煎煮汤剂中，口服后吸收并被递送至循环血浆和肺组织。MIR2911在94%的病毒基因组上均具有结合位点，实验已经证明，其抑制10余种流感病毒、新冠病毒、埃博拉病毒、寨卡病毒、非洲猪瘟病毒的复制，是一种广谱的抗病毒药剂。约10 pmol的MIR2911抑制90%新冠活病毒的复制，是瑞德西韦和羟氯喹等小分子浓度的1/106。siRNA的生物智造昆山杜克大学生物学副教授、全球健康研究中心研究员黄林峰表示：合成生物学技术可用于大规模生产双链RNA，具有经济和环保等独特优势，在RNAi生物农业和生物医药领域具有广阔的应用前景。基于细菌工厂的原核小干扰RNA（pro-siRNA）技术，可大量生产高效和特异的siRNA和高通量生产细胞特异的siRNA文库，实现高效的RNAi靶基因筛选和产品开发。高效mRNA加帽原料LZCap️™的研发恒诺康董事长张健存表示：mRNA的体外制备可以通过酶促或共转录合成。酶促法需要牛痘加帽酶、T7聚合酶以及2-甲基转移化酶多步完成；共转录技术在第三代加帽原料存在下不需使用牛痘加帽酶，可以“一锅”生成Cap1 mRNA。恒诺康开发的新型加帽原料LZCap可以满足“一锅法”制备Cap1 mRNA，比Clean Cap有更高的mRNA产率和蛋白表达量。肿瘤mRNA疫苗研发策略和临床探索研究启辰生联合创始人、CTO栗世铀表示：新冠带给mRNA机遇，时至今日，mRNA的研发热情仍未消退，呈现放量趋势。传染病预防性mRNA中，非COVID-19预防性mRNA疫苗继续强劲增长，迎来黄金增长10年。肿瘤mRNA治疗性疫苗在过往20年全部失败，但现在正逐步进入生产销售阶段，未来将会迎来高速增长。此外，mRNA编码细胞因子、mRNA编码抗体、mRNA蛋白替代制剂研究逐步增加。Beyond COVID-19: A New Era begins with the mRNA Technologym艾博生物执行副总裁袁纪军表示：RNA疫苗在传染性病毒，如COVID-19预防上的有效性已被广泛证明，而在传染病疫苗以外的应用却还没有太多临床验证。肿瘤疫苗是mRNA药物潜在的一个全新的应用场景，mRNA通过树突状细胞将肿瘤特异性抗原蛋白呈递给T细胞，引起免疫系统针对性攻击肿瘤细胞。mRNA药物的自身优势为肿瘤疫苗的开发留下巨大空间。抗肿瘤核酸干扰创新药物的研发和产业化圣诺生物大中华地区CSO杨宪斌表示：RNA干扰疗法具有可成药靶点广泛、安全性高、效果持久，以及开发速度快以及成本相对较低等优势。开发小核酸创新药会面临核酸序列、化学修饰和递送载体三大挑战，众多药企正在寻求突破。抗肿瘤领域的RNA已有众多干扰疗法在研，领先产品已经进入到了临床II期，未来可期。文章来源：同写意推荐阅读BioBAY Talk：对话George Church，畅谈全球生物医药前沿技术与进展15周年丨亘喜生物曹卫：BioBAY的服务精神与专业能力让我印象深刻精英周丨江苏省首家产业创新集群博联中心正式成立

创新药小分子药物信使RNA疫苗基因疗法抗体siRNA细胞疗法

100 项与 MIR2911 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
新型冠状病毒感染	临床申请	中国	江苏命码生物科技有限公司	-
埃博拉病毒性疾病	临床申请	中国	江苏命码生物科技有限公司	-
禽流感	临床申请	中国	江苏命码生物科技有限公司	-
非洲猪瘟	药物发现	中国	南京大学	2022-07-12
寨卡病毒感染	药物发现	中国	南京大学	2022-07-12