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.

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.

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>

Lgr4 Promotes Glioma Cell Proliferation through Activation of Wnt Signaling

Yu, Chun-Yong,Liang, Guo-Biao,Du, Peng,Liu, Yun-Hui Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

The key signaling networks regulating glioma cell proliferation remain poorly defined. The leucine-rich repeat containing G-protein coupled receptor 4 (Lgr4) has been implicated in intestinal, gastric, and epidermal cell functions. We investigated whether Lgr4 functions in glioma cells and found that Lgr4 expression was significantly increased in glioma tissues. In addition, Lgr4 overexpression promoted while its knockdown using small interfering RNA oligos inhibited glioma cell proliferation. In addition, Wnt/${\beta}$-catenin signaling was activated in cells overexpressing Lgr4. Therefore, our results revealed that Lgr4 activates Wnt/${\beta}$-catenin signaling to regulate glioma cell proliferation.

Transcriptome analysis in different chieh‑qua cultivars provides new insights into drought‑stress response

Min Wang,Xiaoming He,Biao Jiang,Wenrui Liu,Yu’e Lin,Dasen Xie,Zhaojun Liang,Lihui Chen,Qingwu Peng 한국식물생명공학회 2019 Plant biotechnology reports Vol.13 No.6

Drought, one of the crucial environmental constraints, seriously threats the quality and yield in chieh-qua. Therefore, cultivat-ing drought-tolerant variety is greatly necessary for its normal growth under water deficiency. However, at present, molecular knowledge on drought resistance is mostly unclear in chieh-qua. In the study, characteristics of two diverse genetic chieh-qua variety, A39 (drought-resistance) and H5 (drought-sensitivity), were analyzed. Under drought stress, H5 exerted high water loss rate, increased malonaldehyde (MDA) content, and decreased enzyme activity of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) compared with A39. In addition, based on the transcriptome results, we obtained a total of 1821 (511 up-regulated and 1310 down-regulated) and 2114 (1282 up-regulated and 832 down- regulated) differentially expressed genes (DEGs) in the A39 versus H5 under normal and water-deficiency stress, respectively. Several DEGs involved in the cuticle synthesis (cytochrome P450 genes: CYP94A2, CYP86B1, CYP86A7), carbohydrate metabolism, and plant hormone signal transduction (small auxin-up RNA genes: SAUR32, SAUR72; JA-induced genes: TIFY 10A, TIFY 10C; ABA related genes: PYL2, PYL4) were explored and related to drought resistance. These expression patterns observed in the RNA-seq data were further confirmed with quantitative real-time PCR (qRT-PCR). In all, these results not only provided a new insight into analyzing genes of drought response, but also laid a foundation for isolating crucial genes involved in drought stress in chieh-qua.

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.

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.