Mechanisms of curcumin-based photodynamic therapy and its effects in combination with electroporation: An in vitro and molecular dynamics study.
- 作者列表："Szlasa W","Szewczyk A","Drąg-Zalesińska M","Czapor-Irzabek H","Michel O","Kiełbik A","Cierluk K","Zalesińska A","Novickij V","Tarek M","Saczko J","Kulbacka J
:Photodynamic therapy (PDT) and electrochemotherapy (ECT) are two methods designed to enhance the anticancer potential of various drugs. Various clinical trials proved the efficacy of both ECT and PDT in melanoma treatment. Curcumin is a natural polyphenolic compound with high anticancer potential against melanoma due to its light absorption properties and toxicity towards cancer cells; however, high reactivity and amphipathic structure of curcumin are limiting its utility. This study aimed to propose the most effective protocol for antimelanoma combination of both therapies (PDT and ECT) in the context of curcumin. The in vitro studies were carried on melanotic melanoma (A375), amelanotic melanoma (C32) and fibroblast (HGF) cell lines. In molecular dynamics studies curcumin presented the single-layer localization in the water-membrane interphase. Further, the mass spectrometry studies exposed that during the PDT treatment curcumin is degraded to vanillin, feruloylmethane, and ferulic acid. Instant ECT with curcumin followed by PDT is the most efficient approach due to its selective genotoxicity towards malignant cells. The metabolic activity of fibroblasts decreased, however, at the same time the fragmentation of DNA did not occur. Additionally, instant PDT with curcumin followed by ECT after 3 h of incubation was a therapy selective towards melanotic melanoma.
: 光动力疗法 (PDT) 和电化疗 (ECT) 是两种旨在增强各种药物抗癌潜力的方法。各种临床试验证明了ECT和PDT在黑素瘤治疗中的功效。姜黄素是一种天然的多酚类化合物，由于其光吸收特性和对癌细胞的毒性，对黑色素瘤具有很高的抗癌潜力; 然而，姜黄素的高反应性和两亲性结构限制了其用途。本研究旨在提出姜黄素背景下两种疗法 (PDT和ECT) 的抗黑色素瘤组合的最有效方案。对黑素瘤 (A375) 、无色素性黑素瘤 (C32) 和成纤维细胞 (HGF) 细胞系进行体外研究。在分子动力学研究中，姜黄素在水-膜间相呈现单层定位。此外，质谱研究表明，在PDT处理期间，姜黄素被降解为香草醛、阿魏酰甲烷和阿魏酸。由于其对恶性细胞的选择性遗传毒性，用姜黄素随后PDT的即时ECT是最有效的方法。然而，成纤维细胞的代谢活性降低，同时没有发生DNA片段化。另外，在孵育3小时后用姜黄素随后ECT的即时PDT是对黑色素黑素瘤的选择性疗法。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.