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.

Collateral Flow in Magnetic Resonance Angiography: Prognostic Value for Vertebrobasilar Stenosis With Stroke Recurrence

Long Yan,Ying Yu,Kaijiang Kang,Zhikai Hou,Min Wan,Weilun Fu,Rongrong Cui,Yongjun Wang,Zhongrong Miao,Xin Lou,Ning Ma 대한신경과학회 2022 Journal of Clinical Neurology Vol.18 No.5

Background and Purpose Intracranial vertebrobasilar atherosclerotic stenosis (IVBAS) is a major cause of posterior circulation stroke. Some patients suffer from stroke recurrence despite receiving medical treatment. This study aimed to determine the prognostic value of a new score for the posterior communicating artery and the P1 segment of the posterior cerebral artery (PCoA-P1) for predicting stroke recurrence in IVBAS. Methods We retrospectively enrolled patients with severe IVBAS (70%–99%). According to the number of stroke recurrences, patients were divided into no-recurrence, single-recurrence, and multiple-recurrences groups. We developed a new 5-point grading scale, with the PCoA-P1 score ranging from 0 to 4 based on magnetic resonance angiography, in which primary collaterals were dichotomized into good (2–4 points) and poor (0 or 1 point). Stroke recurrences after the index stroke were recorded. Patients who did not experience stroke recurrence were compared with those who experienced single or multiple stroke recurrences. Results From January 2012 to December 2019, 176 patients were enrolled, of which 116 (65.9%) had no stroke recurrence, 35 (19.9%) had a single stroke recurrence, and 25 (14.2%) had multiple stroke recurrences. Patients with single stroke recurrence (odds ratio [OR]= 4.134, 95% confidence interval [CI]=1.822–9.380, p=0.001) and multiple stroke recurrences (OR=6.894, 95% CI=2.489–19.092, p<0.001) were more likely to have poor primary collaterals than those with no stroke recurrence. Conclusions The new PCoA-P1 score appears to provide improve predictions of stroke recurrence in patients with IVBAS

On pH and Ca2+ Oscillations Monitored by pH Electrode and Ca-ISE in Bromate–Sulfite–Ferrocyanide System Introduced Ca-EDTA

Shan Yang,Yu Long Hou,Dao Dao Hu 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.1

The pH and Ca2+ oscillations of KBrO3–Na2SO3–K4Fe(CN)6 (BSF) system in presence ofEDTAor Ca-EDTA were investigated. Both EDTA and Ca-EDTA can depress the amplitude and period of pH oscillation, and the effects of Ca-EDTA are more obvious. These effects are attributed to the buffer effect in pH change. The Ca2+ oscillation appears as Ca-EDTAintroduced into the BSF system, which is ascribed to the stability of Ca-EDTA being pH-dependent. The pH and pCa (pCa = −log[Ca2+]) oscillations are synchronous in case of higher concentration of Ca-EDTA; however, the chaotic behavior emerged in pCa oscillation arises at lower pH as the concentration of Ca-EDTA is lower. Such observations can be understood by taking into account the interference of H+ on the response of Ca-ISE to Ca2+. Both amplitude and period for pH and pCa oscillations as KCl introduced into the system can be obviously shortened due to the effect of ion strength on the reaction rate of the core oscillator and on the conditional formation constant of Ca-EDTA. The results are significant for determining whether an experimentally observed chaos in chemical systems is of deterministic origin or is due to experimental noise.

Effect of Abiotic Factors on Fumosorinone Production from Cordyceps fumosorosea via Solid-State Fermentation

Khan Tahir,Hou Dong-Hai,Zhou Jin-Na,Yang Yin-Long,Yu Hong 한국균학회 2023 Mycobiology Vol.51 No.3

Cordyceps fumosorosea is an important species in the genus of Cordyceps, containing a variety of bioactive compounds, including fumosorinone (FU). This study was a ground-breaking assessment of FU levels in liquid and solid cultures. The present study focused on the impacts of solid-state fermentation (SSF) using solid substrates (wheat, oat, and rice), as well as the effects of fermentation parameters (pH, temperature, and incubation period), on the generation of FU. All the fermentation parameters had significant effects on the synthesis of FU. In a study of 25 C, 5.5 pH, and 21 days of incubation period combinations calculated -to give maximal FU production, it was found that the optimal values were 25 C, 5.5 pH, and 21 days, respectively. In a solid substrate medium culture, FU could be produced from SSF. At 30 days, a medium composed of rice yielded the most FU (798.50mg/L), followed by a medium composed of wheat and oats (640.50 and 450.50mg/L), respectively. An efficient method for increasing FU production on a large scale could be found in this approach. The results of this study might have multiple applications in different industrial fermentation processes.

In-pile tritium release behavior and the post-irradiation experiments of Li4SiO4 fabricated by melting process

Zhao Linjie,Yang Mao,Xiao Chengjian,Gong Yu,Ran Guangming,Chen Xiaojun,Li Jiamao,Yue Lei,Chen Chao,Hou Jingwei,Wang Heyi,Long Xinggui,Peng Shuming 한국원자력학회 2024 Nuclear Engineering and Technology Vol.56 No.1

Understanding the tritium release and retention behavior of candidate tritium breeder materials is crucial for breeder blanket design. Recently, a melt spraying process was developed to prepare Li4SiO4 pebbles, which were subsequently subjected to the in-pile tritium production and extraction platform in China Mianyang Research Reactor (CMRR) to investigate their in-situ tritium release behavior and irradiation performance. The results demonstrate that HT is the main tritium release form, and adding hydrogen to the purge gas reduces tritium retention while increasing the HT percent in the purge gas. Post-irradiation experiments reveal that the irradiated pebbles darken in color and their grains swell, but the mechanical properties remain largely unchanged. It is concluded that the tritium residence time of Li4SiO4 made by melt spraying method at 467 ◦C is approximately 23.34 h. High-density Li4SiO4 pebbles exhibit tritium release at relatively low temperatures (<600 ◦C) that is mainly controlled by bulk diffusion. The diffusion coefficient at 525 ◦C and 550 ◦C is 1.19 × 10 11 cm2/s and 5.34 × 10 11 cm2/s, respectively, with corresponding tritium residence times of 21.3 hours and 4.7 hours.

Hypoxia Induced High Expression of Thioredoxin Interacting Protein (TXNIP) in Non-small Cell Lung Cancer and its Prognostic Effect

Li, Yan,Miao, Li-Yun,Xiao, Yong-Long,Huang, Mei,Yu, Min,Meng, Kui,Cai, Hou-Rong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Although associations between thioredoxin interacting protein (TXNIP) and cancers have been recognized, the effects of TXNIP on non-small cell lung cancer (NSCLC) prognosis remained to be determined in detail. In addition, while hypoxia is a key characteristic of tumor cell growth microenvironment, the effect of hypoxia on TXNIP expression is controversial. In this study, formaldehyde fixed and paraffin embedded (FFPE) samples of 70 NSCLC patients who underwent resection between January 2010 and December 2011 were obtained. Evaluation of TXNIP and hypoxia inducible factor-$1{\alpha}$ ($HIF-1{\alpha}$) protein expression in FFPE samples was made by immunohistochemistry. By Kaplan-Meier method, patients with high TXNIP expression demonstrated a significantly shorter progression free survival (PFS) compared with those with low TXNIP expression (18.0 months, 95%CI: 11.7, 24.3 versus 23.0 months, 95%CI: 17.6, 28.4, P=0.02). High TXNIP expression level was also identified as an independent prognostic factor by Cox regression analysis (adjusted hazard ratio: 2.46; 95%CI: 1.08, 5.56; P=0.03). Furthermore, TXNIP expression was found to be significantly correlated with $HIF-1{\alpha}$ expression (Spearman correlation=0.67, P=0.000). To further confirm correlations, we established a tumor cell hypoxic culture model. Expression of TXNIP was up-regulated in all three NSCLC cell lines (A549, SPC-A1, and H1299) under hypoxic conditions. This study suggests that hypoxia induces increased TXNIP expression in NSCLC and high TXNIP expression could be a poor prognostic marker.