miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFκB1

The activation of nuclear factor-kappa B1 (NFkB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for microRNAs (miRNAs) that suppress NFkB1 and observed their effects on radiosensitivity in a human lung cancer cell line. From time series data of miRNA expression in γ-irradiated H1299 human lung cancer cells, we found that the expression of miR-9 was inversely correlated with that of NFκB1. Overexpression of miR-9 down-regulated the level of NFκB1 in H1299 cells, and the surviving fraction of γ-irradiated cells was decreased. Interestingly, let-7g also suppressed the expression of NFκB1, although there was no canonical target site for let-7g in the NFκB1 3' untranslated region. From these results, we conclude that the expression of miR-9 and let-7g could enhance the efficiency of radiotherapy for lung cancer treatment through the inhibition of NFκB1.     

两个取代苄基锡配合物的合成、抗癌活性及其与DNA相互作用

利用二(2,4-二氯苄基)二氯化锡分别与对甲基苯甲酰肼或对叔丁基苯甲酰肼、丙酮酸钠在甲醇中发生反应,合成了2个二(2,4-二氯苄基)锡配合物(C1、C2),通过元素分析、IR、¹H NMR、¹³C NMR、¹¹⁹Sn NMR、HRMS以及X射线单晶衍射表征了配合物结构。测试了配合物C1、C2的热稳定性以及配合物对NCI-H460(人肺癌细胞)、HepG2(人肝癌细胞)和MCF7(人乳腺癌细胞)的体外抑制活性,发现配合物C1对癌细胞均表现较好的抑制作用。利用UV-Vis光谱、荧光光谱以及黏度法研究了2个配合物与ct-DNA之间的相互作用,结果表明配合物是以经典的嵌入模式与DNA结合。     

Polyisoprenylated acylphloroglucinols and a polyisoprenylated tetracyclic xanthone from the bark of Calophyllum thorelii

Two new polyisoprenylated acylphloroglucinols, thoreliones A and B, and a new polyisoprenylated tetracyclic xanthone, oxy-thorelione A, together with twelve known compounds, were isolated from the bark of Calophyllum thorelii. The new structures were determined using spectroscopic methods and chemical modification. The major compound thorelione A (1) showed moderate cytotoxic activity against MCF-7, HeLa and NCI-H460 cells with IC₅₀ values of 7.4, 9.3 and 10.6 μg/mL, respectively, using the sulforhodamine B assay.     

对氯苄基锡酰腙配合物的合成、抗肿瘤活性及其与DNA相互作用

用二对氯苄基二氯化锡分别与对甲基苯甲酰肼缩苯甲酰甲酸及苯甲酰肼缩苯甲酰甲酸反应,合成了2个对氯苄基锡配合物(C1、C2),通过元素分析、IR、1 H NMR、13C NMR、119Sn NMR、HRMS以及X射线单晶衍射等表征了配合物结构。测试了配合物C1、C2的热稳定性以及配合物对癌细胞NCI?H460、HepG2、MCF7的体外抑制活性,发现配合物C2对癌细胞NCI?H460、HepG2、MCF7等均表现出良好的抑制作用。利用紫外吸收光谱、荧光猝灭光谱以及粘度法研究了配合物C2与ct?DNA之间的相互作用,结果表明配合物C2以插入模式与DNA结合。     

LncRNA HSPA7 in human atherosclerotic plaques sponges miR-223 and promotes the proinflammatory vascular smooth muscle cell transition

Although there are many genetic loci in noncoding regions associated with vascular disease, studies on long noncoding RNAs (lncRNAs) discovered from human plaques that affect atherosclerosis have been highly limited. We aimed to identify and functionally validate a lncRNA using human atherosclerotic plaques. Human aortic samples were obtained from patients who underwent aortic surgery, and tissues were classified according to atherosclerotic plaques. RNA was extracted and analyzed for differentially expressed lncRNAs in plaques. Human aortic smooth muscle cells (HASMCs) were stimulated with oxidized low-density lipoprotein (oxLDL) to evaluate the effect of the identified lncRNA on the inflammatory transition of the cells. Among 380 RNAs differentially expressed between the plaque and control tissues, lncRNA HSPA7 was selected and confirmed to show upregulated expression upon oxLDL treatment. HSPA7 knockdown inhibited the migration of HASMCs and the secretion and expression of IL-1β and IL-6; however, HSPA7 knockdown recovered the oxLDL-induced reduction in the expression of contractile markers. Although miR-223 inhibition promoted the activity of Nf-κB and the secretion of inflammatory proteins such as IL-1β and IL-6, HSPA7 knockdown diminished these effects. The effects of miR-223 inhibition and HSPA7 knockdown were also found in THP-1 cell-derived macrophages. The impact of HSPA7 on miR-223 was mediated in an AGO2-dependent manner. HSPA7 is differentially increased in human atheroma and promotes the inflammatory transition of vascular smooth muscle cells by sponging miR-223. For the first time, this study elucidated the molecular mechanism of action of HSPA7, a lncRNA of previously unknown function, in humans.Subject terms: Mechanisms of disease, Atherosclerosis, Long non-coding RNAs     

Citrus sinensis leaf aqueous extract green-synthesized silver nanoparticles: Characterization and cytotoxicity,antioxidant, and anti-human lung carcinoma effects

The present work demonstrates the synthesis of Ag nanoparticles (Ag NPs) by using aqueous extract of Citrus sinensis as green reductant and capping agent without any toxic reagent. Physicochemical characteristics of the said nanoparticles were elucidated by field emission scanning electron microscopy (FESEM), fourier transform infrared spectroscopy (FTIR), and ultraviolet–visible spectroscopy (UV-Vids) techniques. The biogenic Ag NPs are uniformly globular. The Ag NPs has been explored biologically in the anticancer and antioxidant assays. In the cellular and molecular part of the recent study, the treated cells with Ag NPs were assessed by MTT assay for 48 h about the cytotoxicity and anti-human lung carcinoma properties on normal (HUVEC) and lung carcinoma cell lines i.e. NCI-H661, HLC-1, NCI-H1563, LC-2/ad, NCI-H1299, and PC-14. The viability of malignant lung cell line reduced dose-dependently in the presence of Ag NPs. The IC50 of Ag NPs were 82, 139, 170, 66, 62, and 50 µg/mL against NCI-H661, HLC-1, NCI-H1563, LC-2/ad, NCI-H1299, and PC-14 cell lines, respectively. In the antioxidant test, the IC50 of Ag NPs and vitamin E against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals were 21 and 15 µg/mL, respectively. After clinical study, Ag NPs containing Citrus sinensis leaf aqueous extract may be used to formulate a new chemotherapeutic drug or supplement to treat the several types of human lung adenocarcinoma.     

Simultaneous photoelectrochemical detection of dual microRNAs by capturing CdS quantum dots and methylene blue based on target-initiated strand displaced amplification

Herein,we propose a novel photoelectrochemical(PEC) biosensor for dual microRNAs(miRNAs) highly sensitive and simultaneous biosensing based on strand displaced amplification(SDA) reaction.The recognition of H_(miR-21) and H_(let-7 a) by microRNA-21 and let-7 a leads to their change in hairpin structures,subsequently initiating the immobilization of abundant CdS quantum dots(CdS QD s) and methylene blue(MB) based on SDA reaction.The immobilized CdS QDs and MB produce both high PEC currents under430 nm light and 627 nm light illumination,respectively,and the generated PEC currents are closely relied on target miRNAs amounts.Thus,highly sensitive and simultaneous detection of microRNA-21 and let-7 a was readily achieved with detection limit at 6.6 fmol/L and 15.4 fmol/L based on 3σ,respectively.Further,this PEC biosensor was applied in simultaneous analysis of miRNA-21 and let-7 a in breast cancer patient's serum with acceptable results.We expect this biosensor will find more useful application in diagnosis of miRNA-related diseases.     

Cytotoxic principles and α-pyrone ring-opening derivatives of bufadienolides from Kalanchoe hybrida

Purification of the cytotoxic fractions of the methanol extracts of Kalanchoe hybrida leads to three new compounds with the basic skeleton of α-pyrone ring-opening products of bufadienolides, namely, kalanhybrin A-C (1-3). Moreover, four bufadienolides (4-7) and eight other compounds were also characterized from the title plant. The isolated compounds (1-7) were evaluated for their cytotoxicity toward MCF-7, NCI-H460, and SF-268 tumor cell lines. Among them, compounds 4 and 6 displayed significant cytotoxicity toward MCF-7 and NCI-H460 tumor cell lines at the tested concentration. In addition, the biosynthetic pathway of these α-pyrone ring-opening derivatives was also proposed.     

Anti-lung Cancer Activity and Docking Study of Two Novel Isochroman Derivatives

Two new isochroman derivatives(1 and 2) were isolated from the fermentation products of mangrove endophytic fungus Phomopsis sp. 33#. Their structures were characterized by IR, ~1 H NMR, H RMS, and single-crystal X-ray crystallography. The anticancer activity of the two compounds was investigated against four human lung cancer cells(NCI-H292, NCI-H460, LTEP-A-2 and MSTO-211) by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT) assay. Furthermore, molecular docking studies supported the biological assay data, showing that compared with 1, compound 2 has stronger interaction with protein.     

A microwave-assisted stereoselective synthesis of polyandrocarpamines A and B

A stereoselective synthesis of the marine natural products, polyandrocarpamines A and B, has been achieved using a high-yielding one-step aldol condensation reaction under microwave conditions. The structures of both synthetic compounds were confirmed following 1D and 2D NMR, UV, IR and MS spectral analysis, and by comparison with literature data. Both synthetic natural products were assigned Z geometry about their exocyclic double bond on the basis of ¹³C/¹H long-range coupling constants, which were measured using a gHSQMBC experiment. Polyandrocarpamines A and B were evaluated for their cytotoxicity towards the tumour cell lines, MCF-7 (breast), H460 (lung) and SF268 (central nervous system). Polyandrocarpamine A displayed selective cytotoxicity towards the SF268 cell line with a GI₅₀ value of 65 μM.     

Cytotoxic triquinane-type sesquiterpenoids from the endophytic fungus Cerrena sp. A593

Abstract

The culture broth of Cerrena sp. A593, which was isolated from Pogostemon cablin, showed potent cytotoxicity against several human tumor cell lines. The following chemical study resulted in the isolation of two new triquinane-type sesquiterpenoids, named cerrenins D (1) and E (2), along with two known compounds plerocybellone A (3) and chloriolin B (4). Their structures were fully assigned with the aid of extensive spectroscopic analysis (¹H and ¹³C NMR, HSQC, HMBC, ¹H-¹H COSY, HRESIMS, and IR) and data from the literature. Moreover, cytotoxic activity in vitro of compounds 1–4 were evaluated against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. The new compound 1 exhibited weak growth inhibitory activity against all the four tumor cell lines with IC₅₀ values of 41.01, 14.43, 29.67, 44.32?μM.     

Effects of allyl sulfur compounds and garlic extract on the expression of Bcl-2, Bax, and p53 in non small cell lung cancer cell lines

Allyl sulfur compounds play a major role in the chemoprevention against carcinogenesis. The present study compared the antiproliferative effects of diallyl sulfide (DAS), diallyl disulfide (DADS) and garlic extract on p53-wild type H460 and p53-null type H1299 non small cell lung cancer cells (NSCLC). The DAS and DADS treatment of both H460 and H1299 cells resulted in the highest numbers of cells in apoptotic state as measured by acridine orange staining, however, garlic extract treatment did not induce any significant apoptotic cells by MTT assay. DADS was found to be more effective in inducing apoptosis on NSCLC. The level of p53 protein in H460 cell was increased following DADS treatment. DAS and garlic extract treatment of H460 cells induced a rise in the level of Bax and a fall of Bcl-2 level. These results demonstrate that DAS, DADS and garlic extract are effective in reduction of anti-proliferative gene in NSCLC and suggest that modulation of apoptosis-associated cellular proteins by DAS, DADS and garlic extract may be the mechanism for apoptosis which merit further investigation as potential chemoprevention agents.     

Supported silver nanoparticles over alginate-modified magnetic nanoparticles: Synthesis,characterization and treat the human lung carcinoma

This article displays synthesis of Silver nanoparticles (Ag NPs) decorated on sodium alginate covered magnetite (Fe₃O₄/Alg-Ag NPs) nanocomposite. Sodium alginate shell as a natural anionic polysaccharide on Fe₃O₄ microparticles core acted as a stabilizing agent for the reduction of Ag(I) ions into Ag NPs. The structural features of the synthesized nanocomposite were investigated by fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopes (FE-SEM), transmission electron microscopes (TEM), energy-dispersive X-ray spectroscopy (EDX) and vibrating-sample magnetometer (VSM) studies and inductively coupled plasma-optical emission spectroscopy (ICP-OES). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used on common lung cancer cell lines i.e., NCI-H1975, NCI-H1563, and NCI-H1299 to survey the cytotoxicity and anti-lung cancer effects of the synthesized nanocomposite. The synthesized nanocomposite had very low cell viability and high anti-lung cancer activities dose-dependently against NCI-H1975, NCI-H1563, and NCI-H1299 cell lines without any cytotoxicity on the normal cell line (Human umbilical vein endothelial cells (HUVECs)). To determine the antioxidant properties of the synthesized nanocomposite, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was used in the presence of butylated hydroxytoluene as the positive control. The synthesized nanocomposite inhibited half of the DPPH molecules in the concentration of 194 µg/mL. Maybe significant anti-human lung cancer potentials of the synthesized nanocomposite against common human lung cancer cell lines are linked to their antioxidant activities.     

Isolation and structure of five lyngbyabellin derivatives from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula

Five new lyngbyabellin analogs along with a known compound, dolabellin, have been isolated from the marine cyanobacterium Lyngbya majuscula collected from Papua New Guinea. The structures of lyngbyabellins E-I were elucidated through extensive spectroscopic analysis, including HR-FABMS and 1D and 2D NMR experiments. The absolute configurations of lyngbyabellin E and H were ascertained by chiral HPLC and GC/MS analysis of degradation products, in combination with NMR experiments. All five lyngbyabellins showed cytotoxicity to NCI-H460 human lung tumor and neuro-2a mouse neuroblastoma cell lines with LC₅₀ values between 0.2 and 4.8 μM.     

Uses of cyanoacetylhydrazine in heterocyclic synthesis: novel synthesis of pyrazole derivatives with anti-tumor activities

The reaction of cyanoacetylhydrazine with chloroacetyl chloride gave N'-(2-chloroacetyl)-2-cyanoacetohydrazide. The latter underwent cyclization to afford 1-(5 amino-3-hydroxy-1H-pyrazol-1-yl)-2-chloroethanone, which underwent nucleophilic substitution to give 3-(5-amino-3-hydroxy-1H-pyrazol-1-yl)-3-oxopropanenitrile. The latter two compounds were used as key synthons to synthesize new thiophene, pyran, thiazole and some fused heterocyclic derivatives. The antitumor activity of the newly synthesized compounds was evaluated against three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) and some of these compounds were found to exhibit much higher inhibitory effects towards the three tumor cell lines than the Gram positive control doxorubicin.     

2-羰基-3-苯基丙酸芳甲酰腙二(2,4-二氯苄基)锡配合物的合成、晶体结构及生物活性

二(2,4-二氯苄基)二氯化锡分别与2-羰基-3-苯基丙酸苯甲酰腙及2-羰基-3-苯基丙酸水杨酰腙反应,合成了2个取代苄基锡配合物(C1、C2),通过元素分析、IR、1H NMR、13C NMR、119Sn NMR、X射线单晶衍射以及热重分析等表征了配合物结构。测试了配合物对癌细胞Hela、MCF7、Hep G2、Colo205、NCI-H460以及正常人体胚肾细胞HEK293、正常人体肝细胞HL7702的体外抑制活性;在Tris-HCl缓冲溶液中,以EB做为荧光探针,用荧光光谱法初步研究了配合物与小牛胸腺DNA的相互作用。结果表明:配合物C1、C2对5种癌细胞都有明显的抑制作用,配合物C2对HEK293、HL7702的细胞毒性远小于C1;配合物C1与小牛胸腺DNA作用是插入结合与静电结合共同作用所致,配合物C2与小牛胸腺DNA作用是插入结合作用所致。     

Dumbbell probe-mediated cascade isothermal amplification: A novel strategy for label-free detection of microRNAs and its application to real sample assay

Considering the great significance of microRNAs (miRNAs) in cancer detection and typing, the development of sensitive, specific, quantitative, and low-cost methods for the assay of expression levels of miRNAs is desirable. We describe a highly efficient amplification platform for ultrasensitive analysis of miRNA (taking let-7a miRNA as a model analyte) based on a dumbbell probe-mediated cascade isothermal amplification (DP-CIA) strategy. The method relies on the circularization of dumbbell probe by binding target miRNA, followed by rolling circle amplification (RCA) reaction and an autonomous DNA machine performed by nicking/polymerization/displacement cycles that continuously produces single-stranded G-quadruplex to assemble with hemin to generate a color signal. In terms of the high sensitivity (as low as 1 zmol), wide dynamic range (covering 9 orders of magnitude), good specificity (even single-base difference) and easy operation (one probe and three enzymes), the proposed label-free assay is successfully applied to direct detection of let-7a miRNA in real sample (total RNA extracted from human lung tissue), demonstrating an attractive alternative for miRNA analysis for gene expression profiling and molecular diagnostics, particularly for early cancer diagnosis.     

Design,Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety

Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC₅₀ values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure–activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents.     

Biselides A-E: novel polyketides from the Okinawan ascidian Didemnidae sp.

Five new polyketides, biselides A (1), B (2), C (3), D (4), and E (5), were isolated from the Okinawan ascidian Didemnidae sp. Their structures were determined by spectroscopic analysis. Biselides A (1), B (2), and C (3) showed cytotoxicity against human cancer cells NCI-H460 and MDA-MB-231.