Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA

Chunping Yu,Yi Zhang,Ning Wang,Wensu Wei,Ke Cao,Qun Zhang,Peiying Ma,Dan Xie,Pei Wu,Biao Liu,Jiahao Liu,Wei Xiang,Xing Hu,Xuewen Liu,Jianfei Xie,Jin Tang,Zhi Long,Long Wang,Hongliang Zeng,Jianye Liu 한국생체재료학회 2022 생체재료학회지 Vol.26 No.1

Background: Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging. Methods: Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays. Results: The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5’s half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/sicircPRMT5 regulated the miR-30c/SNAIL1/E-adherin axis, inhibiting bladder cancer growth and progression. Conclusion: The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.

Flexural behavior of ultra high performance concrete beams reinforced with high strength steel

Jun-Yan Wang,Jin-Ben Gu,Chao Liu,Yu-Hao Huang,Ru-Cheng Xiao,Biao Ma 국제구조공학회 2022 Structural Engineering and Mechanics, An Int'l Jou Vol.81 No.5

A detailed experimental program was conducted to investigate the flexural behavior of ultra high performance concrete (UHPC) beams reinforced with high strength steel (HSS) rebars with a specified yield strength of 600 MPa via direct tensile test and monotonic four-point bending test. First, two sets of direct tensile test specimens, with the same reinforcement ratio but different yield strength of reinforcement, were fabricated and tested. Subsequently, six simply supported beams, including two plain UHPC beams and four reinforced UHPC beams, were prepared and tested under four-point bending load. The results showed that the balanced-reinforced UHPC beams reinforced with HSS rebars could improve the ultimate loadbearing capacity, deformation capacity, ductility properties, etc. more effectively owing to interaction between high strength of HSS rebar and strain-hardening characteristic of UHPC. In addition, the UHPC with steel rebars kept strain compatibility prior to the yielding of the steel rebar, further satisfied the plane-section assumption. Most importantly, the crack pattern of the UHPC beam reinforced with HSS rebars was prone to transform from single main crack failure corresponding to the normal-strength steel, to multiple main cracks failure under the condition of balanced-reinforced failure, which validated by the conclusion of direct tensile tests cooperated with acoustic emission (AE) source locating technique as well.

Telomerase activity is required for bleomycin-induced pulmonary fibrosis in mice.

Liu, Tianju,Chung, Myoung Ja,Ullenbruch, Matthew,Yu, Hongfeng,Jin, Hong,Hu, Biao,Choi, Yoon Young,Ishikawa, Fuyuki,Phan, Sem H American Society for Clinical Investigation 2007 The Journal of clinical investigation Vol.117 No.12

<P>In addition to its well-known expression in the germline and in cells of certain cancers, telomerase activity is induced in lung fibrosis, although its role in this process is unknown. To identify the pathogenetic importance of telomerase in lung fibrosis, we examined the effects of telomerase reverse transcriptase (TERT) deficiency in a murine model of pulmonary injury. TERT-deficient mice showed significantly reduced lung fibrosis following bleomycin (BLM) insult. This was accompanied by a significant reduction in expression of lung alpha-SMA, a marker of myofibroblast differentiation. Furthermore, lung fibroblasts isolated from BLM-treated TERT-deficient mice showed significantly decreased proliferation and increased apoptosis rates compared with cells isolated from control mice. Transplantation of WT BM into TERT-deficient mice restored BLM-induced lung telomerase activity and fibrosis to WT levels. Conversely, transplantation of BM from TERT-deficient mice into WT recipients resulted in reduced telomerase activity and fibrosis. These findings suggest that induction of telomerase in injured lungs may be caused by BM-derived cells, which appear to play an important role in pulmonary fibrosis. Moreover, TERT induction is associated with increased survival of lung fibroblasts, which favors the development of fibrosis instead of injury resolution.</P>

Discovery of novel glycoside hydrolases from C-glycoside-degrading bacteria using sequence similarity network analysis

Wei Bin,Wang Ya-Kun,Yu Jin-Biao,Wang Si-Jia,Yu Yan-Lei,Xu Xue-Wei,Wang Hong 한국미생물학회 2021 The journal of microbiology Vol.59 No.10

C-Glycosides are an important type of natural product with significant bioactivities, and the C-glycosidic bonds of C-glycosides can be cleaved by several intestinal bacteria, as exemplified by the human faeces-derived puerarin-degrading bacterium Dorea strain PUE. However, glycoside hydrolases in these bacteria, which may be involved in the C-glycosidic bond cleavage of C-glycosides, remain largely unknown. In this study, the genomes of the closest phylogenetic neighbours of five puerarin-degrading intestinal bacteria (including Dorea strain PUE) were retrieved, and the protein-coding genes in the genomes were subjected to sequence similarity network (SSN) analysis. Only four clusters of genes were annotated as glycoside hydrolases and observed in the genome of D. longicatena DSM 13814T (the closest phylogenetic neighbour of Dorea strain PUE); therefore, genes from D. longicatena DSM 13814T belonging to these clusters were selected to overexpress recombinant proteins (CG1, CG2, CG3, and CG4) in Escherichia coli BL21(DE3). In vitro assays indicated that CG4 efficiently cleaved the O-glycosidic bond of daidzin and showed moderate β-D-glucosidase and β-D-xylosidase activity. CG2 showed weak activity in hydrolyzing daidzin and pNP- β-D-fucopyranoside, while CG3 was identified as a highly selective and efficient α-glycosidase. Interestingly, CG3 and CG4 could be selectively inhibited by daidzein, explaining their different performance in kinetic studies. Molecular docking studies predicted the molecular determinants of CG2, CG3, and CG4 in substrate selectivity and inhibition propensity. The present study identified three novel and distinctive glycoside hydrolases, highlighting the potential of SSN in the discovery of novel enzymes from genomic data.

Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate

Xiang Wei,Peng Yongbo,Zeng Hongliang,Yu Chunping,Zhang Qun,Liu Biao,Liu Jiahao,Hu Xing,Wei Wensu,Deng Minhua,Wang Ning,Liu Xuewen,Xie Jianfei,Hou Weibin,Tang Jin,Long Zhi,Wang Long,Liu Jianye 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC.Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays.PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models.These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.

Mitochondrial citrate accumulation drives alveolar epithelial cell necroptosis in lipopolysaccharide-induced acute lung injury

Yang Hui-Hui,Jiang Hui-Ling,Tao Jia-Hao,Zhang Chen-Yu,Xiong Jian-Bing,Yang Jin-Tong,Liu Yu-Biao,Zhong Wen-Jing,Guan Xin-Xin,Duan Jia-Xi,Zhang Yan-Feng,Liu Shao-Kun,Jiang Jian-Xin,Zhou Yong,Guan Cha-Xi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.

Value of contrast-enhanced ultrasonography in microwave ablation treatment of symptomatic focal uterine adenomyosis

Xiao-Long Li,Jia-Xin Li,Song-Yuan Yu,Pei-Li Fan,Yun-Jie Jin,Er-Jiao Xu,Sai-Nan Guan,Er-Ya Deng,Qiu-Yan Li,Zheng-Biao Ji,Jiu-Ling Qi,Hui-Xiong Xu,China Alliance of Multi-Center Clinical Study for Ultra 대한초음파의학회 2024 ULTRASONOGRAPHY Vol.43 No.1

Purpose: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis.Methods: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up.Results: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered.Conclusion: CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes. Purpose: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. Methods: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCE- MRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. Results: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. Conclusion: CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pre- treatment CEUS indicates satisfactory treatment outcomes.