Polyelectrolyte Oil‐Core Nanocarriers for Localized and Sustained Delivery of Daunorubicin to Colon Carcinoma MC38 Cells: The Case of Polysaccharide Multilayer Film in Relation to PEG‐ylated Shell

The authors examine properties of daunorubicin (DNR)‐loaded oil‐core multilayer nanocapsules prepared via layer‐by‐layer approach with different polyelectrolyte (PE) coatings such as a standard one (containing polysodium 4‐styrenesulphonate/poly(diallyldimethyl‐ammonium) chloride) and a polysaccharide‐based shell (dextran/chitosan), in regard to the outer layer of poly‐l ‐glutamic acid (PGA) grafted with polyethylene glycol (PGA‐g‐PEG). The nanocarriers are obtained on a cationic nanoemulsion template (stabilized by dicephalic‐type surfactant, N ,N‐bis[3,30‐(trimethylammonio)propyl]‐dodecanamide dimethylsulfate) and layered with the PE shell of different thicknesses resulting in average size of 150 nm in diameter (as shown by dynamic light scattering, scanning electron microscopy and cryogenic‐transmission electron microscopy, and atomic force microscopy). The nanocapsules demonstrate efficient DNR encapsulation and its sustained release under physiological conditions or in the attendance of human serum albumin. The biocompatibility studies using colon carcinoma MC38 and macrophage P388D1 cell lines as well as human erythrocytes reveal that surface charge and outer PE layer type determine nanocarrier features that control their biological activity: protein adsorption, cellular internalization and localization, induction of apoptosis, and hemolytic activity. The investigations indicate that polysaccharide‐coated nanocapsules present a considerable potential for application as efficient DNR delivery systems in chemotherapy of colon cancer as an alternative to nanocarriers with PEG‐ylated shell.

     

Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling

ObjectiveTo explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling.MethodsGene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes.ResultsIn this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway − oxidative phosphorylation.ConclusionsWe identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC.     

Phytochemical profiling,molecular docking,and in vitro anti-hepatocellular carcinoid bioactivity of Suaeda vermiculata extracts

The ATP-binding cassette is the major class of transporters responsible for the efflux of chemotherapeutic agents from cancer cells, resulting in treatment failures of cancer’s patients. Suaeda vermiculata Forssk. ex. J. F. Gmel. is traditionally known for its liver protective activity. The LC-MS based chemical profilings of the sequentially partitioned sub-extracts obtained from the alcoholic extract of S. vermiculata using n-hexane, chloroform, ethyl acetate, and n-butanol as fractionating solvents, identified a total of thirty six compounds. These sub-extracts were evaluated for their anti-hepatocarcinoma activity against the sensitive HepG2 and doxorubicin (DOX)-resistant, HepG-2/ADR cell lines. A mixture of doxorubicin and sub-extracts at 20 μg/ml doses were also tested for their anti-hepatocarcinoma activity. The exhibited IC₅₀ values for the chloroform, ethyl acetate, n-hexane, and n-butanol sub-extracts, and the doxorubicin against HepG2, and HepG-2/ADR cell lines were found at 64.5, 66.8, 81.25, 125, 1.3 μg/ml, and 110.1, 91.82, 138.2, 265.7, 4.77 μg/ml levels, respectively. However, the treatment of resistant cells with 20 μg/ml of different sub-extracts in combination with the doxorubicin showed significant improvements in the doxorubicin activity against the resistant cells, and the IC₅₀ values for DOX + chloroform, DOX + ethyl acetate, DOX + n-hexane, and DOX + n-butanol against resistant cells, were at 1.77, 2.05, 2.66, and 2.71 μg/ml levels, respectively. The IC₅₀ values exhibited 2.69x, 2.33x, 1.79x and 1.76x-folds reversal of the sensitivity in the resistant cancer cell lines. The molecular docking studies of the compounds identified in the LC-MS chemical profilings, against three ATP-binding cassette proteins i.e., ABCB1, ABCC1, and ABCG2, showed that flavonoids as the major class of compounds responsible for reversal of the resistant cells sensitivities. The predicted binding affinity for the flavonoids against the above mentioned three ATP-binding cassette proteins’ are in the ranges of ～?8 to ?11 kcal/mol. Our results clearly indicate that the presence of flavonoids, as the major class of compounds in the S. vermiculata is responsible for the chemosensitization of the resistant HCC-cell lines. Moreover, the structures, 21 (5‐O‐methyl visamminol), 22 (N-trans-feruloyl tyramine), 27 (atractylenolide-III), and 32 (ginsenoside-Rh2) were also identified among the potential ATP-binding cassette’s modulators during the current study. These observations put the S. vermiculata in perspective with the traditionally claimed liver protective efficacy of the plant.     

The ethnobotanical,phytochemistry and pharmacological activities of Psidium guajava L.

Psidium guajava L., commonly known as guava is an important tropical food plant with diverse medicinal values. In traditional medicine, it is used in the treatment of various diseases such as diarrhoea, diabetes, rheumatism, ulcers, malaria, cough, and bacterial infections. The aim of this review is to provide up-to-date information on the ethnomedicinal uses, bioactive compounds, and pharmacological activities of P. guajava with greater emphasis on its therapeutic potentials. The bioactive constituents extracted from P. guajava include phytochemicals (gallic acid, casuariin, catechin, chlorogenic acid, rutin, vanillic acid, quercetin, syringic acid, kaempferol, apigenin, cinnamic acid, luteolin, quercetin-3-O-α-L-arabinopyranoside, morin, ellagic acid, guaijaverin, pedunculoside, asiastic acid, ursolic acid, oleanolic acid, methyl gallate and epicatechin) and essential oils (limonene, trans-caryophyllene, α-humulene, γ-muurolene, selinene, caryophyllene oxide, bisabolol, isocaryophyllene, δ-cadinene, α-copaene, α-cedrene, β-eudesmol, α-pinene, β-pinene, β-myrcene, linalool, α-terpineol and eucalyptol). In vitro and in vivo studies demonstrated that P. guajava possesses pharmacological activities such as antidiabetic, antidiarrhoeal, hepatoprotective, anticancer, antioxidant, anti-inflammatory, antiestrogenic, and antibacterial activities which support its traditional uses. The exhibited pharmacological activities reported may be attributed to the numerous bioactive compounds present in different parts of P. guajava. Based on the beneficial effects of P. guajava as well as its bioactive constituents, it can be exploited in the development of pharmaceutical products and functional foods. However, there is a need for comprehensive studies in clinical trials to establish the safe doses and efficacy of P. guajava for the treatment of several diseases.     

柴胡逆转肝细胞癌多药耐药作用与相关机制的研究

选用对VCR天然耐药肝癌细胞株Bel-7402为对象来研究柴胡逆转MDR效果与相关的机制,以寻找一种新型的具有多药耐药逆转活性的中药.结果表明,柴胡具有逆转肝细胞癌多药耐药作用,并与抗癌药物VCR有协同作用.柴胡对人肝癌Bel-7402细胞株具有多药耐药逆转作用,提高了耐药细胞内的VCR含量,增加了VCR对细胞G2期阻滞作用,抑制了P-170糖蛋白的表达,抑制MDR1/mRNA的表达,提高了TopoαmRNA水平.     

胃癌与七种元素关系的分析

57例胃癌癌灶内锌值为(13.740±4.150)×10~(-6),低于癌边缘组织(15.677±4.567)×10~(-6)(P<0.01),亦低于正常组织(15.897±3.580)×10~(-6)(P<0.01)。癌灶铜值为(7.91±6.19)×10~(-6),高于正常组织(5.62±12.01)×10~(-6)(P<0.05),癌灶铜/锌比值亦高于正常组织(P<0.01),但与边缘组织无显著性差异。分化较好的胃腺癌与未分化癌间七种微量元素含量均无显著性差异。这些结果提示,胃癌组织中锌值的降低与铜/锌比值的升高可作为胃癌的辅助诊断指标,而且锌值的检测更具意义。但与分化程度无关。     

Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells

Pancreatic carcinoma still represents one of the most lethal malignant diseases in the world although some progress has been made in treating the disease in the past decades. Current multi-agent treatment options have improved the overall survival of patients, however, more effective treatment strategies are still needed. In this paper we have characterized the anticancer potential of coumarin-palladium(II) complex against pancreatic carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being effective at micromolar concentrations (0.5 μM). Treatments induced apoptosis, increased BAX/BCL-2 ratio and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma xenografts resulted in significant reduction in tumor mass, without provoking any adverse toxic effects including hepatotoxicity. Presented results indicate the great potential of the tested compound and the perspective of its further development towards pancreatic cancer therapy.