ML216-Induced BLM Helicase Inhibition Sensitizes PCa Cells to the DNA-Crosslinking Agent Cisplatin

Using standard DNA-damaging medicines with DNA repair inhibitors is a promising anticancer tool to achieve better therapeutic responses and reduce therapy-related side effects. Cell viability assay, neutral comet assay, western blotting (WB), and cell cycle and apoptosis analysis were used to determine the synergistic effect and mechanism of ML216, a Bloom syndrome protein (BLM) helicase inhibitor, and cisplatin (CDDP), a DNA-crosslinking agent, in PCa cells. Based on the online database research, our findings revealed that BLM was substantially expressed in PCa, which is associated with a bad prognosis for PCa patients. The combination of ML216 and CDDP improved the antiproliferative properties of three PCa cell lines. As indicated by the increased production of γH2AX and caspase-3 cleavage, ML216 significantly reduced the DNA damage-induced high expression of BLM, making PC3 more susceptible to apoptosis and DNA damage caused by CDDP. Furthermore, the combination of ML216 and CDDP increased p-Chk1 and p-Chk2 expression. The DNA damage may have triggered the ATR-Chk1 and ATM-Chk2 pathways simultaneously. Our results demonstrated that ML216 and CDDP combination therapy exhibited synergistic effects, and combination chemotherapy could be a novel anticancer tactic.     

Prodigiosin Sensitizes Sensitive and Resistant Urothelial Carcinoma Cells to Cisplatin Treatment

Cisplatin-based treatment is the standard of care therapy for urothelial carcinomas. However, complex cisplatin resistance mechanisms limit the success of this approach. Both apoptosis and autophagy have been shown to contribute to this resistance. Prodigiosin, a secondary metabolite from various bacteria, exerts different biological activities including the modulation of these two cellular stress response pathways. We analyzed the effect of prodigiosin on protein levels of different autophagy- and apoptosis-related proteins in cisplatin-sensitive and -resistant urothelial carcinoma cells (UCCs). Furthermore, we investigated the effect on cell viability of prodigiosin alone or in combination with cisplatin. We made use of four different pairs of cisplatin-sensitive and -resistant UCCs. We found that prodigiosin blocked autophagy in UCCs and re-sensitized cisplatin-resistant cells to apoptotic cell death. Furthermore, we found that prodigiosin is a potent anticancer agent with nanomolar IC₅₀ values in all tested UCCs. In combination studies, we observed that prodigiosin sensitized both cisplatin-sensitive and -resistant urothelial carcinoma cell lines to cisplatin treatment with synergistic effects in most tested cell lines. These effects of prodigiosin are at least partially mediated by altering lysosomal function, since we detected reduced activities of cathepsin B and L. We propose that prodigiosin is a promising candidate for the therapy of cisplatin-resistant urothelial carcinomas, either as a single agent or in combinatory therapeutic approaches.     

Alternative Approach for Specific Tyrosinase Inhibitor Screening: Uncompetitive Inhibition of Tyrosinase by Moringa oleifera

Tyrosinase (TYR) is a type III copper oxidase present in fungi, plants and animals. The inhibitor of human TYR plays a vital role in pharmaceutical and cosmetic fields by preventing synthesis of melanin in the skin. To search for an effective TYR inhibitor from various plant extracts, a kinetic study of TYR inhibition was performed with mushroom TYR. Among Panax ginseng, Alpinia galanga, Vitis vinifera and Moringa oleifera, the extracts of V. vinifera seed, A. galanga rhizome and M. oleifera leaf reversibly inhibited TYR diphenolase activity with IC₅₀ values of 94.8 ± 0.2 µg/mL, 105.4 ± 0.2 µg/mL and 121.3 ± 0.4 µg/mL, respectively. Under the same conditions, the IC₅₀ values of the representative TYR inhibitors of ascorbic acid and kojic acid were found at 235.7 ± 1.0 and 192.3 ± 0.4 µg/mL, respectively. An inhibition kinetics study demonstrated mixed-type inhibition of TYR diphenolase by A. galanga and V. vinifera, whereas a rare uncompetitive inhibition pattern was found from M. oleifera with an inhibition constant of K_ii 73 µg/mL. Phytochemical investigation by HPLC-MS proposed luteolin as a specific TYR diphenolase ES complex inhibitor, which was confirmed by the inhibition kinetics of luteolin. The results clearly showed that studying TYR inhibition kinetics with plant extract mixtures can be utilized for the screening of specific TYR inhibitors.     

Cordycepin Sensitizes Cholangiocarcinoma Cells to Be Killed by Natural Killer-92 (NK-92) Cells

Immunotherapy harnessing immune functions is a promising strategy for cancer treatment. Tumor sensitization is one approach to enhance tumor cell susceptibility to immune cell cytotoxicity that can be used in combination with immunotherapy to achieve therapeutic efficiency. Cordycepin, a bioactive compound that can be extracted from some Cordyceps spp. has been reported to effectively inhibit tumor growth, however, the mechanism of its tumor sensitization activity that enhances immune cell cytotoxicity is unknown. In the present study, we investigated the potency of cordycepin to sensitize a lethal cancer, cholangiocarcinoma (CCA), to natural killer (NK) cells. Treatment with cordycepin prior to and during co-culturing with NK-92 cells significantly increased cell death of KKU-213A as compared to solitary cordycepin or NK treatment. Moreover, sensitization activity was also observed in the combination of NK-92 cells and Cordyceps militaris extract that contained cordycepin as a major component. The cordycepin treatment remarkably caused an increase in TRAIL receptor (DR4 and DR5) expression in KKU-213A, suggesting the possible involvement of TRAIL signaling in KKU-213A sensitization to NK-92 cells. In conclusion, this is the first report on the sensitization activity of cordycepin on CCA cells to NK cytotoxicity, which supports that cordycepin can be further developed as an alternate immunomodulating agent.     

Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.     

Scale Inhibition of Green Inhibitor Polyepoxysuccinic Sodium

Polyepoxysuccinic acid (PESA) is the green water treatment agents recognized all over the world[1-3]. It is found that when PESA is used alone, it had good scale inhibition. PESA should be included in the category of green scale inhibitor.PESA is synthesized with maleicanhydride in the presence of catalysts. The effect on scale-in-hibiting property of the product from amount and feed times of catalyst, the reaction temperature, the reaction time were investigated. The optimum reaction conditions are as follows:n(maleic anhydride):n(Ca(OH)2):n(NaOH)=1:0.05-0.2:0.5, reaction temperature 95C, reaction time 4h.In all the references about PESA, PESA is researched as a kind of highly effective scale inhibitor or chelate. In this paper, the performance of scale inhibition of PESA is evaluated by scale static inhibitor.The results are shown in Figture1.It is evident from our experimental data (Figture1) that when inhibition for CaCO3.With the increase of PESA dosage, scale inhibition increases. When dosage is more than 6mg/L, inhibition efficiency is over 50%. The formulas give scale inhibition efficiency more than 95% at 12mg/L of total dosage.     

Selective Targeting of Tumor and Stromal Cells By a Nanocarrier System Displaying Lipidated Cathepsin B Inhibitor

Cathepsin B (CtsB) is a lysosomal cysteine proteinase that is specifically translocated to the extracellular milieu during cancer progression. The development of a lipidated CtsB inhibitor incorporated into the envelope of a liposomal nanocarrier (LNC‐NS‐629) is described. Ex vivo and in vivo studies confirmed selective targeting and internalization of LNC‐NS‐629 by tumor and stromal cells, thus validating CtsB targeting as a highly promising approach to cancer diagnosis and treatment.     

Linear Adsorption Enables NO Selective Electroreduction to Hydroxylamine on Single Co Sites

Hydroxylamine (NH₂OH), a vital industrial feedstock, is presently synthesized under harsh conditions with serious environmental and energy concerns. Electrocatalytic nitric oxide (NO) reduction is attractive for the production of hydroxylamine under ambient conditions. However, hydroxylamine selectivity is limited by the competitive reaction of ammonia production. Herein, we regulate the adsorption configuration of NO by adjusting the atomic structure of catalysts to control the product selectivity. Co single-atom catalysts show state-of-the-art NH₂OH selectivity from NO electroreduction under neutral conditions (FE : 81.3 %), while Co nanoparticles are inclined to generate ammonia (FE : 92.3 %). A series of in situ characterizations and theoretical simulations unveil that linear adsorption of NO on isolated Co sites enables hydroxylamine formation and bridge adsorption of NO on adjacent Co sites induces the production of ammonia.     

Corrosion Inhibition of a Green Scale Inhibitor Polyepoxysuccinic Acid

The corrosion inhibition of a green scale inhibitor, polyepoxysuccinic acid (PESA) was studied based on dynamic tests. It is found that when PESA is used alone, it had good corrosion inhibition. So, PESA should be included in the category of corrosion inhibitors. It is not only a kind of green scale inhibitor, but also a green corrosion inhibitor. The synergistic effect betweenPESA and Zn2 or sodium gluconate is poor. However, the synergistic effect among PESA, Zn2 and sodium gluconate is excellent, and the corrosion inhibition efficiency for carbon steel is higher than 99%. Further study of corrosion inhibition mechanism reveals that corrosion inhibition of PESA is not affected by carboxyl group, but by the oxygen atom inserted. The existence of oxygen atom in PESA molecular structure makes it easy to form stable chelate with pentacyclic     

Spectroscopic Identification of Active Sites of Oxygen-Doped Carbon for Selective Oxygen Reduction to Hydrogen Peroxide

The electrochemical synthesis of hydrogen peroxide (H₂O₂) via a two-electron (2 e⁻) oxygen reduction reaction (ORR) process provides a promising alternative to replace the energy-intensive anthraquinone process. Herein, we develop a facile template-protected strategy to synthesize a highly active quinone-rich porous carbon catalyst for H₂O₂ electrochemical production. The optimized PCC₉₀₀ material exhibits remarkable activity and selectivity, of which the onset potential reaches 0.83 V vs. reversible hydrogen electrode in 0.1 M KOH and the H₂O₂ selectivity is over 95 % in a wide potential range. Comprehensive synchrotron-based near-edge X-ray absorption fine structure (NEXAFS) spectroscopy combined with electrocatalytic characterizations reveals the positive correlation between quinone content and 2 e⁻ ORR performance. The effectiveness of chair-form quinone groups as the most efficient active sites is highlighted by the molecule-mimic strategy and theoretical analysis.     

Potential of Kalopanax septemlobus Leaf Extract in Synthesis of Silver Nanoparticles for Selective Inhibition of Specific Bacterial Strain in Mixed Culture

Silver nanoparticles (AgNPs) were synthesised using Kalopanax septemlobus plant leaf extracts. UV-visible spectrophotometric, Fourier-transform infrared, electron dispersive X-ray spectroscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses confirmed synthesis of AgNPs. TEM micrographs revealed presence of well-dispersed AgNPs predominantly of small size and different shapes with an average particle size of 30.8 nm. Antimicrobial susceptibility tests of AgNP treatments revealed variability in sensitivity of bacteria Bacillus cereus and Saccharophagus degradans under study. Minimum inhibitory concentration (MIC) values of the AgNPs for B. cereus and S. degradans were found to be 30 and 10 μg/mL, respectively. The mixed culture of B. cereus and S. degradans treated with AgNPs at 10 μg/mL showed increase in growth with time, suggesting survival of bacteria in liquid media. The plating of mixed culture before AgNP treatment showed presence of both bacteria, but 24-h-old mixed culture treated with AgNPs at the concentration of 10 μg/mL showed presence of B. cereus colonies. SEM micrographs revealed damage to S. degradans cells but no effect on B. cereus cells after AgNP treatment. Confocal microscopic observations of AgNP-treated mixed cultures by Nile blue A staining indicated intact polyhydroxyalkanoates producing flourescent cells of B. cereus but damage and deformities in S. degradans cells. This study suggests that AgNPs can selectively inhibit growth of S. degradans and retain B. cereus at MIC of S. degradans. This report is a case study for selective inhibition of one bacteria and growth of the other in a culture using plant-synthesized silver nanoparticles.     

Directing Topoisomerase I Mediated DNA Cleavage to Specific Sites by Camptothecin Tethered to Minor- and Major-Groove Ligands

No Abstract     

多点位吸附型咪唑啉季铵盐缓蚀剂的合成及其缓蚀性能

以对二甲氨基苯甲酸、二乙烯三胺和氯化苄为原料,两步法合成了一种新型具有多个潜在吸附中心的季铵盐型咪唑啉缓蚀剂（MIQ）,利用傅里叶变换红外光谱对合成的产物进行了表征。 通过失重法研究了该缓蚀剂在6%盐酸溶液中对碳钢的缓蚀性能。 讨论了缓蚀剂用量、温度、时间对缓蚀性能的影响,并研究了其与某些物质复配后的协同作用。 结果表明,合成的季铵盐型咪唑啉缓蚀剂在6%的盐酸腐蚀环境中,用量为0.5%时对碳钢的缓蚀率可达97%以上,缓蚀率随温度的升高和时间的延长而降低。 MIQ与乌洛托品、KSCN以及KI等复配后可以显著改善缓蚀剂的缓蚀率。 从吸附等温线推测,该缓蚀剂抑制腐蚀的机理是缓蚀剂在碳钢表面吸附成膜,进而有效阻挡了碳钢表面与酸性清洗试剂的接触。     

HDAC6选择性抑制剂WT161的合成工艺优化

本文报道了一条新的合成HDAC6选择性抑制剂WT161的路线。以辛二酸单甲酯为起始原料,经缩合、取代、还原、脱水共四步反应得到HDAC6选择性抑制剂WT161,总收率64.8%,目标产物结构均经过~1HNMR、~(13)CNMR和HRMS等确证。优化后的工艺路线原料成本低、反应条件温和、反应后处理更简单、产物收率更高,比较适合较大规模制备。