汤湖热矿泥中微量元素的分析及其作用

用原子吸收分光光度法测定了汤湖热矿泥中锌、铅、铁、钙、镁、锰、．硒、铜、 砷的含量,并对其在泥疗中的作用进行了探讨。     

pH药物控释的氮掺杂碳点载运阿霉素用于光热与化疗的协同治疗

提出一种利用氮掺杂碳点(N-CDs)的光热性能与化疗药物阿霉素(Dox)相结合的联合治疗肿瘤模式。实验结果标明,所制备的N-CDs的分散液经光照后升温可达10℃,是性能优异的光热剂。同时,载运Dox后的N-CDs-Dox纳米复合物还具有pH触发的药物控释作用。因此,这种多功能的N-CDs-Dox纳米复合物能够实现光热和化疗的协同作用,有效杀伤肿瘤细胞。     

聚多巴胺-阿霉素纳米颗粒对癌细胞的化疗-光热治疗协同作用

通过在水相中加入乙醇和氨水, 将单分子多巴胺聚合成具有良好光热转换能力的聚多巴胺纳米颗粒(PDA), 并利用π-π作用与共价键作用, 将抗癌药物阿霉素(Dox)负载到聚多巴胺纳米颗粒的表面, 制备了聚多巴胺纳米颗粒负载阿霉素(PDA-Dox), 研究了PDA-Dox的药物缓释性能. 结果发现, PDA-Dox能够在酸性环境下增加药物释放. 细胞实验显示, PDA-Dox配合激光照射, 能够通过化疗和光热治疗高效地杀死癌细胞.     

电感耦合等离子体质谱法(ICP-MS)测定汤岗子热矿泥黑粉中16种矿物元素

对汤岗子热矿泥黑粉中矿物元素进行了分析研究。用微波消解法处理汤岗子热矿泥黑粉样品,采用ICP-MS法对热矿泥黑粉中16种元素进行分析。结果表明,在优化实验条件下,方法的检出限为0.00028～14.66μg/L,相对标准偏差为0.18%～6.20%,回收率为91.5%～108.2%。为探讨汤岗子热矿泥黑粉对人体的保健作用提供了参考数据。     

阿霉素—铁（Ⅲ）配合物的电化学特征及其与DNA结合作用研究

采用示波极谱法环伏安法研究了３价铁离子Ｆｅ（Ⅲ）与阿霉素（ＡＤＭ）配合物 电化学特性。在生理ｐＨ条件下，Ｆｅ（Ⅲ）与ＡＤＭ形成２：１的稳定配合物，Ｆｅ（Ⅲ）配位使ＡＤＭ在更负的电势下才能还原，这与其心脏毒性减轻密切相关，采用线性扫描，吸收光谱和凝胶电泳法研究了ＡＤＭ－Ｆｅ（Ⅲ）配合物与ＤＮＡ的结合作用，ＡＤＭ－Ｆｅ（Ⅱ）栩合物仍保留了ＡＤＭ插入结合的特征，并形成一种稳定的ＤＮＡ－Ｆｅ（Ⅲ）－ＡＤＭ     

基于DNA纳米花的细胞自噬基因沉默用于增敏抗肿瘤化疗

自噬是真核细胞降解蛋白质的重要途径之一, 在细胞的更新代谢中起重要作用. 肿瘤细胞借助高水平的细胞自噬能够阻断细胞凋亡途径, 降低化疗药物的抗肿瘤效果. 本文通过设计编码有核酸适配体序列(Aptamer)和DNA酶序列(DNAzyme)的多功能DNA纳米花, 利用DNA序列可负载化疗药物阿霉素(Dox)的特性, 实现了对肿瘤细胞特异靶向的药物递送, 并高效沉默肿瘤细胞的自噬相关基因ATG5, 达到增敏抗肿瘤化疗的效果. 通过RT-PCR实验验证合成的DNA纳米花可以有效剪切肿瘤细胞中自噬相关基因ATG5的mRNA; 并通过DNA纳米花的细胞毒性和细胞凋亡实验研究了其对肿瘤细胞系MCF-7的靶向治疗作用, 结果显示该多功能DNA纳米花在增敏抗肿瘤化疗方面具有明显优势.     

具有强烈杀伤肿瘤细胞活性的新抗肿瘤抗生素C1027分子作用机制

本研究表明,C1027是以细胞内染色质或染色体DNA为靶体,直接造成核小体连接区DNA损伤,损伤的方式包括DNA单链断裂、双链断裂及单链断裂合并互补链上相邻断裂口部位出现无碱基位点,C1027损伤细胞DNA的作用显著强于新制癌菌素,平阳霉素,阿霉素及丝裂霉素C,本文还从分子机制的水平讨论了C1027强烈细胞毒性。     

汤岗子热矿泥黑粉中16种矿物元素的分析

对汤岗子热矿泥黑粉中16种矿物元素进行分析研究。用微波消解法处理汤岗子热矿泥黑粉样品, 采用电感耦合等离子体质谱法对汤岗子热矿泥黑粉中钠、镁、钾、钙、铁、锌、锰、铜、锗、钼、铬、铝、镍、砷、汞、铅等16种矿物元素进行分析。结果表明, 在优化实验条件下, 方法的检出限为0.00028-14.66 μg/L , 相对标准偏差为0.18%-6.20 %, 回收率为91.5 %～108.2%。为探讨汤岗子热矿泥黑粉对人体的保健作用提供参考。     

C_(70)富勒醇对小鼠心脏毒性的研究

研究C_(70)富勒醇(简写为C_(70)-OH)在常规治疗剂量下对小鼠心脏功能的影响。通过对小鼠行为学的观察和对心脏系数、血生化指标、心脏组织病理学和组织透射等的检测,结果显示常用的小分子血管阻断剂康普瑞汀磷酸二钠(CA4P)对心肌有明显损伤,而C_(70)-OH未表现出明显的心脏毒性。     

药物心脏毒性基团模型的构建

本文根据文献报道的已知药物对hERG的阻滞活性数据,运用Catalyst软件构建了可以初步预测药物心脏毒性作用的模型,并根据该模型得到的结构特征分析了药物具有hERG阻滞活性的结构特点,以便研究者在药物设计过程中进行合理规避,减小药物开发初期的投入。本研究构建的药物心脏毒性基团模型具有四个特征：两个芳环叠合中心,一个静电中心以及一个疏水中心。各项评价参数和验证数据均显示该模型具有良好的心脏毒性预测能力（图1）。     

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

Doxorubicin is a widely used and promising anticancer drug; however, a severe dose-dependent cardiotoxicity hampers its therapeutic value. Doxorubicin may cause acute and chronic issues, depending on the duration of toxicity. In clinical practice, the accumulative toxic dose is up to 400 mg/m² and increasing the dose will increase the probability of cardiac toxicity. Several molecular mechanisms underlying the pathogenesis of doxorubicin cardiotoxicity have been proposed, including oxidative stress, topoisomerase beta II inhibition, mitochondrial dysfunction, Ca²⁺ homeostasis dysregulation, intracellular iron accumulation, ensuing cell death (apoptosis and necrosis), autophagy, and myofibrillar disarray and loss. Natural products including flavonoids have been widely studied both in cell, animal, and human models which proves that flavonoids alleviate cardiac toxicity caused by doxorubicin. This review comprehensively summarizes cardioprotective activity flavonoids including quercetin, luteolin, rutin, apigenin, naringenin, and hesperidin against doxorubicin, both in in vitro and in vivo models.     

Stability and iron coordination in DNA adducts of Anthracycline based anti-cancer drugs

There is evidence that the interaction of the α-ketol group of the Doxorubicin and Epirubicin anti-cancer drugs with Fe(iii) generates hydroxyl radicals under aerobic conditions, causing cardiotoxicity in patients. Considering that the formation of DNA adducts is one of the main targets of Anthracycline drugs, we have in the present study characterized several [Anthracycline-DNA]Fe(iii) complexes with respect to their stability and Fe(iii) coordination, by means of MD simulations. Iron is found to coordinate well to the drugs containing an α-ketol group, this being the only group of the drug that binds to the metal. The complexes containing an α-ketol group, [Doxorubicin-DNA]Fe(iii) and [Epirubicin-DNA]Fe(iii), thus show greater stability than those not containing it, i.e., [Daunorubicin-DNA]Fe(iii), [Idarubicin-DNA]Fe(iii) and [5-Imino-Daunorubicin]Fe(iii). Metal attachment to the α-ketol group is furthermore facilitated by the phosphate groups of DNA. The coordination to iron in the [Doxorubicin-DNA]Fe(iii) system is smaller than that found for the [Epirubicin-DNA]Fe(iii) system, and the corresponding number of coordinating waters in the former is larger than in the latter. This may in turn result in higher hydroxyl radical production, thus explaining the increased cardiotoxicity noted for Doxorubicin.     

Antioxidant and Protective Effects of <Emphasis Type="Italic">Schinus terebinthifolius</Emphasis> Raddi Against Doxorubicin-Induced Toxicity

Doxorubicin is an anticancer drug whose toxic effects on non-cancer cells are associated with increased oxidative stress. This study investigated the chemical composition, antioxidant activity of the methanolic extract of Schinus terebinthifolius Raddi leaves (MESL) as well as effects against doxorubicin-induced toxicity in human erythrocytes, K562 human erythroleukemia cells, and mouse hearts. The chemical composition indicated the presence of phenolic compounds, flavonoids, tannins, and ascorbic acid. MESL showed antioxidant activity by scavenging free radicals and inhibiting hemolysis and lipid peroxidation in human erythrocytes incubated with an oxidizing agent, and was able to increase the enzymatic activity of superoxide dismutase and glutathione peroxidase in human erythrocytes, without influencing the activity of enzyme catalase. The increase of oxidative hemolysis and malondialdehyde levels in erythrocytes incubated with doxorubicin was reduced by treatment with MESL. The cytotoxic activity of doxorubicin in erythroleukemia cells treated with MESL was unmodified. Additionally, the extract protected mice against the doxorubicin-induced cardiotoxicity. In conclusion, the MESL exhibits antioxidant activity, reducing doxorubicin-induced oxidative stress without changing the anticancer action of the drug, and protects against doxorubicin-induced cardiotoxicity. Hence, these findings suggest that these effects are via anti-oxidative by inhibiting free radicals, decreased oxidative stress, and increased antioxidant enzyme activity.     

Specific Targeting of PEGylated Liposomal Doxorubicin (Doxil®) to Tumour Cells Using a Novel TIMP3 Peptide

Doxorubicin is a cytotoxic anthracycline derivative that has been used as a chemotherapeutic in many different forms of human cancer with some success. However, doxorubicin treatment has several side-effects, the most serious of which is cardiomyopathy, that can be fatal. Doxorubicin encapsulation in PEGylated liposomes (Doxil^®) has been shown to increase tumour localisation and decrease cardiotoxicity. Conversely, the stability of such liposomes also leads to increased circulation times and accumulation in the skin, resulting in palmar planter erythrodysesthesia, while also limiting release of the drug at the tumour site. Specific targeting of such liposomes to tumour cells has been attempted using various receptor-specific peptides and antibodies. However, targeting a single epitope limits the likely number of tumour targets and increases the risk of tumour resistance through mutation. In this report, Doxil^® was coupled to peptide sequence p700 derived from tissue inhibitor of metalloproteinase 3. This Doxil^® -P700 complex results in an approximately 100-fold increase in drug uptake, relative to Doxil^® alone, by both mouse and human breast cancer cells and immortalised vascular cells resulting in an increase in cytotoxicity. Using p700 to target liposomes in this way may enable specific delivery of doxorubicin or other drugs to a broad range of cancers.     

Albumin-Albumin/Lactosylated Core-Shell Nanoparticles: Therapy to Treat Hepatocellular Carcinoma for Controlled Delivery of Doxorubicin

Doxorubicin (Dox) is the most widely used chemotherapeutic agent and is considered a highly powerful and broad-spectrum for cancer treatment. However, its application is compromised by the cumulative side effect of dose-dependent cardiotoxicity. Because of this, targeted drug delivery systems (DDS) are currently being explored in an attempt to reduce Dox systemic side-effects. In this study, DDS targeting hepatocellular carcinoma (HCC) has been designed, specifically to the asialoglycoprotein receptor (ASGPR). Dox-loaded albumin-albumin/lactosylated (core-shell) nanoparticles (tBSA/BSALac NPs) with low (LC) and high (HC) crosslink using glutaraldehyde were synthesized. Nanoparticles presented spherical shapes with a size distribution of 257 ± 14 nm and 254 ± 14 nm, as well as an estimated surface charge of −28.0 ± 0.1 mV and −26.0 ± 0.2 mV, respectively. The encapsulation efficiency of Dox for the two types of nanoparticles was higher than 80%. The in vitro drug release results showed a sustained and controlled release profile. Additionally, the nanoparticles were revealed to be biocompatible with red blood cells (RBCs) and human liver cancer cells (HepG2 cells). In cytotoxicity assays, Dox-loaded nanoparticles decrease cell viability more efficiently than free Dox. Specific biorecognition assays confirmed the interaction between nanoparticles and HepG2 cells, especially with ASGPRs. Both types of nanoparticles may be possible DDS specifically targeting HCC, thus reducing side effects, mainly cardiotoxicity. Therefore, improving the quality of life from patients during chemotherapy.     

Protective Effect of Two Alkaloids from Hippophae rhamnoides Linn. against Doxorubicin-Induced Toxicity in H9c2 Cardiomyoblasts

Background: Doxorubicin (Dox) is one of the most frequently prescribed anti-cancer drugs. However, clinical application with Dox is limited due to its potentially fatal cumulative cardiotoxicity. N-p-coumaroyl-4-aminobutan-1-ol (alk-A), an organic amide alkaloid and hippophamide (alk-B), a rare pyridoindole alkaloid were successfully obtained by purification and separation of seabuckthorn seed residue in our previous research. This study was undertaken to investigate the protective effect of alk-A and alk-B against Dox-induced embryonic rat cardiac cells (H9c2 cells) apoptosis. Methods: H9c2 cells were treated with Dox (2.5 µM) in the presence of alk-A and alk-B (10, 20, and 40 µM) and incubated for 24 h. Results: It was shown that pretreatment of the H9c2 cells with alk-A and alk-B significantly reduced Dox-induced apoptosis. Alk-A and alk-B both inhibited reactive oxygen species (ROS) production and suppressed cleaved-caspase-3 protein expression and the activation of JNK (Jun N-terminal kinases), as well as increasing ATP levels, favoring mitochondrial mitofusin protein expression, and relieving damage to mitochondrial DNA. Conclusions: These results suggest that alk-A and alk-B can inhibit Dox-induced apoptosis in H9C2 cardiac muscle cells via inhibition of cell apoptosis and improvement of mitochondrial function, while alk-B showed more protection. Alk-B could be a potential candidate agent for protecting against cardiotoxicity in Dox-exposed patients.     

Hydrophilic interaction and reversed‐phase ultra‐performance liquid chromatography TOF‐MS for metabolomic analysis of Veratrum nigrum‐induced cardiotoxicity

The acute cardiotoxicity induced by Veratrum nigrum (VN) is explored by analyzing heart tissue metabolic profiles in mouse models and applying reversed‐phase liquid chromatography mass spectrometry and hydrophilic interaction liquid chromatography mass spectrometry that are based on ultra‐high‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry. An animal model of acute heart injury was established in mice via intra‐gastric administration of VN. Then, electrocardiogram and echocardiograph monitoring of cardiac function and pathological examination were performed on mice in both the control and VN groups, and it was verified that acute heart injury was caused. Meanwhile, comparing the results of the control and VN groups, we detected 36 differential endogenous metabolites of heart tissue, including taurine, riboflavin, purine and lipids, which are related to many possible pathways such as purine metabolism, taurine and hypotaurine metabolism and energy metabolism. Our study provides a scientific approach for evaluating and revealing the mechanisms of VN‐induced cardiotoxicity via the metabolomic strategy.     

Functionalization of Polyethyleneimine with Hollow Cyclotriveratrylene and Its Subsequent Supramolecular Interaction with Doxorubicin

In this paper, a modified Cyclotriveratrylene was synthesized and linked to a branched Polyethylenimine, and this unique polymeric material was subsequently examined as a potential supramolecular carrier for Doxorubicin. Spectroscopic analysis in different solvents had shown that Doxorubicin was coordinated within the hollow-shaped unit of the armed Cyclotriveratrylene, and the nature of the host–guest complex revealed intrinsic Van der Waals interactions and hydrogen bonding between the host and guest. The strongest interaction was detected in water because of the hydrophobic effect shared between the aromatic groups of the Doxorubicin and Cyclotriveratrylene unit. Density functional theory calculations had also confirmed that in the most stable coordination of Doxorubicin with the cross-linked polymer, the aromatic rings of the Doxorubicin were localized toward the Cyclotriveratrylene core, while its aliphatic chains aligned closer with amino groups, thus forming a compact supramolecular assembly that may confer a shielding effect on Doxorubicin. These observations had emphasized the importance of supramolecular considerations when designing a novel drug delivery platform.