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

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

OBJECTIVETo 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.METHODSWe 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.RESULTSAfter 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).CONCLUSIONLb-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, Ying ; Zhang, Yi ; Yang, Xingbin ; Qin, Xinshu ; Xu, Ke ; Xin, Yirao ; Wang, Jianing ; Xu, Qin ; Li, Yinglei ; Wang, Xingyu

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.

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适应症	最高研发状态	国家/地区	公司	日期
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
新型冠状病毒感染	药物发现	中国	江苏命码生物科技有限公司	-
埃博拉病毒性疾病	药物发现	中国	江苏命码生物科技有限公司	-
禽流感	药物发现	中国	江苏命码生物科技有限公司	-