China
Africa
Explore chapters and articles related to this topic
Nanoparticle-Mediated Small RNA Deliveries for Molecular Therapies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ramasamy Paulmurugan, Uday Kumar Sukumar, Tarik F. Massoud
Effective overexpression strategies are needed to examine the effects of miRNA-directed regulation of gene expression in vivo. AntagomiRs or anti-miRs are small chemically modified antisense oligonucleotides that are used to block the function of endogenous miRNAs. They inhibit miRNA activity by irreversibly binding to target miRNA [119]. Specific miRNAs can be silenced by anti-miRNAs complementary to the mature miRNA sequences [120]. Each miRNA controls the expression of numerous target genes by blocking translation of the target protein, and about 200 target genes may be regulated by a single miRNA [121]. AntagomiRs are effective silencers of miRNA function expression in mice. AntagomiR-122 has been used to specifically silence the function of miR-122 in the lung, liver, skin, intestine, heart, and bone marrow of normal mice. The effect of targeted gene silencing was found to last for more than a week after a single intravenous injection [119, 121]. We have previously shown that delivery of anti-sense miRNAs blocking the function of endogenous miR-21 and miR-10b by PLGA nanoparticles can prevent metastasis while showing significant antitumor effect in triple negative breast cancer in vivo in small animal models (Figure 13.6) [4].
Can we accelerate the osteoporotic bone fracture healing response?
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Martijn van Griensven, Elizabeth Rosado Balmayor
Thus, in osteoporotic fractures, microRNAs can be upregulated that (1) inhibit the formation of bone-forming cells and/or bone-forming activity and (2) inhibit osteoclast-inhibiting proteins. Therefore, these microRNAs are detrimental for fracture healing in osteoporotic patients. Blocking these upregulated microRNAs would be a possible mechanism to ameliorate the negative effects and improve fracture healing. Inhibition of microRNAs can be achieved by using “antagomirs.” Antagomirs are complementary RNA strands that bind to the active microRNA strand and then either degrade or block the binding to the target messenger RNA sequence. Subsequently, the microRNA cannot bind to its complementary messenger RNA, and there is no interference with the translation of the target messenger RNA into protein. The delivery of antagomirs is similar to the delivery in gene therapy. Antagomir delivery has been investigated in an array of different mammalian cells (48,49). It has also been used in in vivo models targeting different tissues such as brain and liver (50–52). The first clinical studies are being conducted using antagomir-122 for treating hepatitis C (53,54).
The mitotic phase of spermatogenesis
Published in C. Yan Cheng, Spermatogenesis, 2018
He et al. have compared miRNA expression in GFRα1+ and GFRα1– population by microarray. They have identified miR-20 and miR-106a as two miRNAs preferentially expressed in GFRα1+ spermatogonia and in spermatogonial cell line C18-4. Transfection of miRNA mimics for these two miRNAs can each promote the proliferation/self-renewal of SSCs as reflected by the increased BrdU uptake, the increased expression of proliferation marker PCNA and self-renewal marker Plzf, and the increased SSC activity as measured by transplantation assay. Consistent with the gain-of-function model, antagomir against these two miRNAs can each inhibit SSC numbers and activity. Further studies have identified Stat3 and Ccnd1 as the downstream targets of miR-20 and 106a that contribute to SSC self-renewal.93
Downregulation of miR-761 ameliorates radiation-induced pulmonary fibrosis by regulating PGC-1α
Published in Experimental Lung Research, 2022
Zeng Wang, Junying Chen, Li Su, Jinsheng Hong
A total of 80 Eight-week-old female C57BL/6 mice (body weight 18–20 g) were obtained from the Shanghai SLAC Laboratory Animal Co. Ltd (SLAC Co. Ltd., Shanghai, China). Mice were housed five per cage (ten mice per group), in standard laboratory conditions and fed with sterilized food and water ad libitum. Half of these mice were used to examine the expression of miR-761 after irradiation, and the remainders were used to verify the protective effect of inhibition of miR-761 on pulmonary fibrosis. Mice were placed in a specifically designed, well-ventilated plastic box and given a single dose (15 Gy) of X-rays at a dose rate of 2 Gy/min to the whole thorax. Antagomir761 was applied to suppress the expression of miR-761 in animal experiments (Antagomir has been documented by numerous studies to be highly effective in knocking down target miRNA with long-lasting efficacy under in vivo conditions22) 200 μL volume Antagomir761 (10 mg/kg body weight) or AntagomirNC was administered by tail vein injection weekly for 24 weeks from the day of irradiation. Antagomir were purchased from Shanghai GenePharma Company (Shanghai, China). Animals were treated in accordance with the guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health, and approved by the local animal care committee. All of the animal experiments were reviewed and approved by the Ethics Committee of Fujian Medical University.
MiR-494-mediated Effects on the NF-κB Signaling Pathway Regulate Lipopolysaccharide-Induced Acute Kidney Injury in Mice
Published in Immunological Investigations, 2022
Peng Lu, Lei Zhang, Ting Liu, Jing-Jing Fan, Xu Luo, Yi-Tang Zhu
The Mice (n = 24) were randomized into four groups with six in each group: the Control group, the LPS group, LPS + scrambled antagomir group, and LPS + miR-494 antagomir group. LPS (8 mg/kg) was intraperitoneally (i.p.) injected into each mouse in the LPS groups (Islam et al. 2019), while those in the Control group received an equal volume of saline. The LPS was extracted from Bacillus coli O111:B4. Approximately 30 min after LPS injection, mice in the LPS + scrambled antagomir group, and the LPS + miR-494 antagomir group were injected intravenously (i.v.) with the mixture of 60 μL miR-494 antagomir (5ʹ-TCCCGTGTATGTTTC-3ʹ, 20 µmol/L, Ribobo, Guangzhou, China) or scrambled antagomir (5ʹ-ACGTCTATACGCCCA-3ʹ, 20 µmol/L, Ribobo, Guangzhou, China) with 60 μL transfection reagent, respectively. The dose of miR-494 antagomir and scrambled antagomir were chosen based on the previous study (Zhao et al. 2020). The mice in the other groups were given an equal volume of normal saline. Twenty-four hours later, blood samples were collected for the analysis of the kidney function parameters [blood urea nitrogen (BUN) and serum creatinine (Cr)] with a Roche Cobas C311 Chemistry Analyzer (Roche Diagnostics, Indianapolis, IN, USA). Then, the kidney tissues were collected after mice sacrificed via cervical dislocation. And the kidneys were weighed, washed with saline, and stored for further analysis. The kidney index was measured to be kidney weight/body weight × 100 (g/100 g body weight).
MiR-140-5p exerts a protective function in pregnancy-induced hypertension via mediating TGF-β/Smad signaling pathway
Published in Hypertension in Pregnancy, 2022
Ji-Yun Li, Yan Jin, Yan-Min Cao, Gui-Mei Wu
To induce PIH syndrome in rats, 40 male and 40 female rats were kept in each cage (1:1) during the estrus. In every morning, vaginal secretion smear of female rats was observed and the date when vaginal suppository was found was recorded as day 1 of gestation (16). Then, the pregnancy rats were divided into four groups: normal group (normal pregnancy rats), PIH group (PIH model rats), PIH + agomiR-140-5p group (PIH rats injected with agomiR-140-5p), and PIH + antagomiR-140-5p group (PIH rats injected with antagomiR-140-5p), with 10 rats in each group. PIH rats were subcutaneously injected with l-nitro-arginine methylester (L-NAME) (Sigma, US) by 50 mg/kg/d from day 14 to day 19 (16). AgomiR-140-5p or antagomiR-140-5p (GenePharma, China) was injected from the tail veins of rats on day 13 of gestation at a rate of 100 μL/day (6 days) in rats from PIH + agomiR-140-5p or antagomiR-140-5p group (17), while those in the PIH group was injected with an equal volume of normal saline.