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1.
Nianxiu Duan Junjun Li Sha Song Feng Wang Yiwei Yang Di Nie Caifen Wang Yingjie Sheng Yali Tao Jie Gao Can Xu Yan Wei Yong Gan 《Advanced functional materials》2021,31(46):2100605
Tumor-specific enhanced delivery of chemotherapeutics and modulators to tumor cells and activated pancreatic stellate cells (aPSCs), respectively, represents safer and more effective therapy for pancreatic cancer. Herein, a membrane type 1-matrix metalloproteinase (MT1-MMP)-cleavable spacer is used to assemble low-density cRGDfK onto thermosensitive liposomes loaded with phosphorylated calcipotriol (PCAL) and doxorubicin (DOX), yielding MR-T-PD. The liposome-linked cRGDfK prodrug on MR-T-PD surface is first activated by MT1-MMP, which is selectively expressed on tumor endothelial cells, to release cRGDfK. The free cRGDfK specifically promotes tumor angiogenesis, leading to 3.4-fold higher accumulation and a wider distribution of MR-T-PD in tumors. Furthermore, MR-T-PD rapidly releases PCAL and DOX into the interstitium under heat treatment. The released DOX enters tumor cells to induce apoptosis, whereas the PCAL prodrug is converted to CAL by alkaline phosphatase on the surface of aPSCs; CAL can then enter aPSCs to induce quiescence and promote the antitumor effect of DOX. Finally, by enhancing the exposure of DOX and CAL to tumor cells and aPSCs, respectively, in a tumor-specific manner, MR-T-PD exerts superior efficacy (a 5.9-fold decrease in tumor weight) without causing additional side effects. Overall, this prodrug-based smart liposome system represents a promising paradigm for pancreatic cancer therapy. 相似文献
2.
Yu-Hung Lee Ching-Fang Yu Ying-Chieh Yang Ji-Hong Hong Chi-Shiun Chiang 《International journal of molecular sciences》2021,22(4)
The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade. 相似文献
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4.
以链脲佐菌素(Streptozotocin,STZ)诱导的糖尿病小鼠为研究对象,研究短链脂肪酸对糖尿病小鼠血糖代谢的改善作用。通过腹腔注射200 mg/kg STZ建立糖尿病小鼠模型,研究乙酸钠、丙酸钠和丁酸钠对糖尿病小鼠进食量和体重变化、口服葡萄糖耐量(OGTT)、血糖水平、血清胰岛素水平、胰岛素抵抗(HOMA-IR)、胰岛β细胞功能(HOMA-β)指数及胰腺组织结构的影响。结果显示:与模型组相比,乙酸钠和丙酸钠可显著降低累计进食量(p0.05),分别降低了10.09%和8.90%;乙酸钠和丁酸钠,对2型糖尿病小鼠其他指标包括体重、空腹血糖、葡萄糖耐量、胰岛素抵抗和胰腺组织损伤修复都没有显著改善作用(p0.05)。丙酸钠可以显著降低血糖水平(20.65%)和胰岛素抵抗(11.19%),增强胰岛β细胞功能(64.50%),提高葡萄糖耐量,对胰腺组织损伤起到改善作用。 相似文献
5.
Jan Bilski Agnieszka Irena Mazur-Bialy Marcin Surmiak Magdalena Hubalewska-Mazgaj Janusz Pokorski Jacek Nitecki Ewa Nitecka Joanna Pokorska Aneta Targosz Agata Ptak-Belowska Jerzy A. Zoladz Tomasz Brzozowski 《International journal of molecular sciences》2020,21(22)
Physical exercise is known to influence hormonal mediators of appetite, but the effect of short-term maximal intensity exercise on plasma levels of appetite hormones and cytokines has been little studied. We investigated the effect of a 30 s Wingate Test, followed by a postprandial period, on appetite sensations, food intake, and appetite hormones. Twenty-six physically active young males rated their subjective feelings of hunger, prospective food consumption, and fatigue on visual analogue scales at baseline, after exercise was completed, and during the postprandial period. Blood samples were obtained for the measurement of nesfatin-1, ghrelin, leptin, insulin, pancreatic polypeptide (PP), human growth factor (hGH) and cytokine interleukin-6 (IL-6), irisin and plasma lactate concentrations, at 30 min before exercise, immediately (210 s) after exercise, and 30 min following a meal and at corresponding times in control sedentary males without ad libitum meal intake, respectively. Appetite perceptions and food intake were decreased in response to exercise. Plasma levels of irisin, IL-6, lactate, nesfatin-1 and ghrelin was increased after exercise and then it was returned to postprandial/control period in both groups. A significant rise in plasma insulin, hGH and PP levels after exercise was observed while meal intake potentiated this response. In conclusion, an acute short-term fatiguing exercise can transiently suppress hunger sensations and food intake in humans. We postulate that this physiological response involves exercise-induced alterations in plasma hormones and the release of myokines such as irisin and IL-6, and supports the notion of existence of the skeletal muscle–brain–gut axis. Nevertheless, the detailed relationship between acute exercise releasing myokines, appetite sensations and impairment of this axis leading to several diseases should be further examined. 相似文献
6.
Mohamed Abdin Yahya Saud Hamed Hafiz Muhammad Saleem Akhtar Dan Chen Shanza Mukhtar Peng Wan Asad Riaz Xiaoxiong Zeng 《International Journal of Food Science & Technology》2019,54(6):2084-2093
The objectives of this study were to determine the optimal extraction conditions of polyphenols from Syzygium cumini seeds by response surface methodology and investigate their antioxidant activity and inhibition on α-amylase and pancreatic lipase. As results, the optimal extraction conditions in the ultrasonic extraction process which maximised total polyphenols content, minimised the IC50 values of α-amylase and pancreatic lipase were determined as follows: extraction time 60 min, ethanol concentration 63% and solvent/solid ratio 44 mL g−1. The main phenolic compounds in partially purified fraction of Syzygium cumini seeds were catechin, epicatechin, kaempferol, gallic, 5-caffeoylquinic, caffeic and ferulic acids. In addition, the partially purified fraction inhibited 87.66 ± 5.55 and 86.61 ± 3.15% of α-amylase and pancreatic lipase, respectively. The results suggested that Syzygium cumini seeds could be explored as a natural antioxidant and could be used as a source of highly antidiabetic and anti-obesity bioactive compounds. 相似文献
7.
在分析板栗壳黄酮结构的基础上,研究其对胰脂肪酶的抑制作用及类型。采用醇提法提取板栗壳中的黄酮,并用AB-8大孔吸附树脂进行纯化,冻干后得到的黄酮含量为(107.50±1.00)mg/g,提取得率为(5.66±0.05)%。利用超高效液相色谱-四极杆/静电场轨道阱质谱联用技术对板栗壳黄酮进行结构分析,鉴定出8 种黄酮类化合物。采用对硝基苯酚法测定胰脂肪酶活力,分别考察板栗壳黄酮对胰脂肪酶的抑制效果及不同反应条件下板栗壳黄酮对胰脂肪酶活性的影响,结果表明,板栗壳黄酮对胰脂肪酶有较好的抑制作用,半抑制浓度(half maximal inhibitory concentration,IC50)为0.074 mg/mL,且使胰脂肪酶最适pH值向碱性偏移。通过Lineweaver-Burk双倒数作图法确定其抑制类型为非竞争性抑制,抑制常数Ki=53.19 mg/mL。由此可见,板栗壳黄酮是一种效果良好的胰脂肪酶抑制剂。 相似文献
8.
Charles E. Carraher Jr. Michael R. Roner Anthony G. Campbell Alisa Moric-Johnson Lindsey Miller Paul Slawek 《国际聚合物材料杂志》2018,67(8):469-479
Polyesters were formed from the reaction of the salt of camphoric acid and Group IVB metallocene dichlorides using the interfacial polycondenzation process. The polyesters were formed in good yields with moderate chain lengths. Fourier transform infrared spectroscopy shows bands characteristic of the presence of both reactants with new bands characteristic of the formation of the M?O and M–O(CO) linkage present. The polymers largely exist in a bridging geometry of the carbonyl groups about the metal atom. Nuclear magnetic resonance shows the presence of bands derived from both reactants. Matrix-assisted laser desorption/ionization mass spectroscopy shows ion fragments to three units for the polymers with isotopic abundance characteristic of the presence of metal atoms in the ion fragment clusters. All the polymers exhibit good ability to inhibit all the tested cancer cell lines but the zironocene and hafnocene polymers exhibit especially good inhibition of the tested cancer cell lines that included two pancreatic cancer cell lines. They represent a potential new group of anticancer drugs. 相似文献
9.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
10.
不规则三角网是影响土石方量计算的关键问题之一,虽然目前已有大量研究人员对Delaunay三角网进行优化,但仍然缺少对三角网生成速率和计算精度的综合研究。针对此问题,基于VB.NET平台的点、边以及三角形的结构化数据结构设计快速生成凸闭包集形成Delaunay三角网,通过四边形空圆特性以及对角线最短原则对构网结果进行检验和优化。试验计算表明,该算法的计算结果与经典DTM法、方格网法的土方量计算相对误差均在0.30%以内。该方法不仅具有较高的组网效率,并能保持较好的计算精度。 相似文献