Safflor yellow A protects vascular endothelial cells from ox-LDL-mediated damage.

Atherosclerosis is a chronic disease of arteries, which constitutes the pathological basis of a series of cardiovascular diseases. The inflammatory response of vascular endothelial cells mediated by oxidized low density lipoprotein (ox-LDL) is the early behavior and main signal of atherosclerosis. In this study, the damage model of vascular endothelial cells treated with ox-LDL was used to reproduce the damage process of vascular endothelial cells in the process of atherosclerosis. Cell viability was detected by CCK-8. The release levels of reactive oxygen species, nitric oxide, and superoxide dismutase (SOD) were detected by commercial kits. EdU cell proliferation assay was used to detect cell proliferation, real-time fluorescent quantitative PCR and Western blot were used to detect the expression level of related genes. The results showed we successfully constructed a vascular endothelial injury model by incubating vascular endothelial cells with gradient concentrations of ox-LDL. The incubation of safflor yellow A (SYA) partially restored the loss of viability of vascular endothelial cells mediated by ox-LDL, and SYA could promote the proliferation of injured vascular endothelial cells. In addition, SYA may transmit related signals through the AMPK pathway to protect vascular endothelial cells from ox-LDL-mediated damage. All these results provide a further understanding of the occurrence and development of atherosclerosis, provide a theoretical basis for the use of SYA-related drugs in the treatment of cardiovascular diseases, and provide a reference paradigm for studying the pharmacology, toxicology, and mechanism of action of key active substances in TCM.

STAT3/miR-15a-5p/CX3CL1 Loop Regulates Proliferation and Migration of Vascular Endothelial Cells in Atherosclerosis.

Endothelial cell proliferation disorder caused by vascular injury seems to be one of the causes of atherosclerosis, which is the pathological basis of coronary heart disease. The role of STAT3 in the regulation of microRNAs and endothelial dysfunction in atherosclerosis is unclear. STAT3 can be activated by cytokine IL-6 and up regulate the expression of CX3CL1. In addition, microRNA-15a-5p (miR-15a-5p) inhibited the transcription of CX3CL1, the proliferation of vascular endothelial cells and the proliferation of STAT3 regulated vascular endothelial cells. STAT3 positively regulates the expression of CX3CL1, and then down-regulates the inhibition of CX3CL1 by over-expression of miR-15a-5p, thus forming an elimination feedback loop to control the proliferation of HUVECs and affect the progression of atherosclerosis. In conclusion, miR-15a-5p may be the therapeutic target of the pathological basis of coronary atherosclerosis.

Long noncoding RNA H19 competitively binds miR-93-5p to regulate STAT3 expression in breast cancer.

The long noncoding RNA H19 is overexpressed in many cancers and acts as an oncogene. Here, we explored the role of H19 in breast cancer cells, including the effect of H19 on proliferation, migration, and invasion of breast cancer cells. We also investigated the relation of H19 to microRNA miR-93-5p and signal transducers and activators of transcription 3 (STAT3), the target gene of miR-93-5p. Ectopic expression of H19 in MCF-7 cells and knockdown of H19 in MDA-MB-231 cells showed that overexpression of H19 promoted proliferation, migration, and invasion, whereas knockdown of H19 reduced proliferation, migration, and invasion in vitro. Dual-luciferase reporter assays and RNA-binding protein immunoprecipitation assays proved that H19 was a target of miR-93-5p. In addition, H19 antagonized the downregulation of miR-93-5p on its target STAT3 and antagonized miR-93-5p-mediated cell proliferation. Our study revealed a new network in the expression of STAT3 involving H19 and miR-93-5p, which may contribute to a better understanding of breast cancer pathogenesis and provide new insights into the treatment of this disease.

MKL1/miR34a/FOXP3 axis regulates cell proliferation in gastric cancer.

Megakaryoblastic leukemia 1 (MKL1) was closely related to the pathogenesis of various human malignant cancers. MiR34a was reported to be closely related to cancer cell proliferation. Forkhead box protein 3 (FOXP3) was a transcription factor that played a different role in different cancer types. CDK6 was involved in cell cycle progression and was upregulated in several types of cancers. The present study investigated the effects of MKL1/miR34a/FOXP3 axis on cell proliferation in MGC803 gastric cancer cells. Our results demonstrated that overexpression of MKL1 promoted proliferation of MGC80-3 cells, MKL1 directly binding to the promoter of CDK6 to increase its expression. Knockdown of FOXP3 promoted proliferation of MGC80-3 cells and MKL1 inhibited the expression of FOXP3 via miR-34a. The finding can contribute to elucidating the regulatory mechanism involved in the cell cycle progression of gastric cancer cells and may aid in screening potential gene targets for the biological therapy of gastric cancer.

PKM2 promotes glucose metabolism through a let-7a-5p/Stat3/hnRNP-A1 regulatory feedback loop in breast cancer cells.

Tumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions than normal cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for tumor cell aerobic glycolysis. We established a role for let-7a-5p/Stat3/hnRNP-A1/PKM2 signaling in breast cancer cell glucose metabolism. PKM2 depletion via small interfering RNA (siRNA) inhibits cell proliferation and aerobic glycolysis in breast cancer cells. Signal transducer and activator of transcription 3 (Stat3) promotes upregulation of heterogeneous nuclear ribonucleoprotein (hnRNP)-A1 expression, hnRNP-A1 binding to pyruvate kinase isoenzyme (PKM) pre messenger RNA, and the subsequent formation of PKM2. This pathway is downregulated by the microRNA let-7a-5p, which functionally targets Stat3, whereas hnRNP-A1 blocks the biogenesis of let-7a-5p to counteract its ability to downregulate the Stat3/hnRNP-A1/PKM2 signaling pathway. The downregulation of Stat3/hnRNP-A1/PKM2 by let-7a-5p is verified using a breast cancer. These results suggest that let-7a-5p, Stat3, and hnRNP-A1 form a feedback loop, thereby regulating PKM2 expression to modulate glucose metabolism of breast cancer cells. These findings elucidate a new pathway mediating aerobic glycolysis in breast cancers and provide an attractive potential target for breast cancer therapeutic intervention.

The strong competitive role of 2n pollen in several polyploidy hybridizations in Rosa hybrida.

BACKGROUND: 2n pollen play a strong competitive role in hybridization and breeding of multiploids in Rosa hybrida. The ploidy inheritable characteristic of 'Orange Fire' × 'Old Blush' were analyzed. RESULT: The results of the cytological observations indicated that 2n pollen developed from the defeated cytoplasmic division or nuclear division in the meiosis metaphase II of PMC (pollen mother cell) in 'Old Blush'. The natural generation rate of the 2n pollen in 'Old Blush' (2x) was about 1.39 in percentage of all male gametes, whereas the tetraploids in the F1 offspring possessed a high rate, i.e., 44.00%. The temporal and spatial characteristics of 'Old Blush' pollen germination on the stigma and growth in pistil of 'Orange Fire' and 'DEE' were observed, and the results suggested that the germination rate of 2n pollen on the stigma was not superior to that of 1n pollen, but that the proportion of 2n pollen increased to 30.90 and 37.20%, respectively, while it traversed the stigma and entered into style. The callose plug in the 2n pollen tube was significantly thinner than that of 1n pollen tube. And each trait involved in our experiment probably is very important for F1 morphological phenotypes. CONCLUSION: We conclude that 2n pollen are involved in hybridization and have a competitive advantage while it traversed the stigma and entered into style. The callose plug in the 2n pollen tube was may have strongly influenced the competitive process in R. hybrida.

Monodisperse Bismuth-Halide Double Perovskite Nanocrystals Confined in Mesoporous Silica Templates.

Metal halide perovskites have fascinating electronic properties and have already been implemented in various devices. Although the behavior of the properties of lead halide perovskite nanocrystals has been studied, the properties of lead-free perovskite nanocrystals are less well-understood because synthesizing them is still very challenging. Here, a simple and popularizable method has been demonstrated to grow monodisperse bismuth-halide double perovskite nanocrystals, Cs2AgBiBr6 (1), inside three kinds of mesoporous silica templates. The size and morphology of nanocrystals depend on the structure and pore size of the template. Structural analysis shows that the nanocrystals of various sizes and morphologies retain the crystal structure of bimetallic perovskite. 1 exhibits different morphologies in the silicon channels of three templates: square nanoparticles in KIT-6, spherical and rodlike particles in SBA-15, and nanowires in MCM-41. UV-vis-NIR and photoluminescence measurements show us the variation of band gap and carrier recombination time due to quantum confinement of nanocrystals in mesoporous silicon materials. The band gaps of nanocrystals in the template exhibit an obvious blue shift compared with that of the bulk sample, and the carrier recombination time is significantly shortened. We show that mesoporous silicon templates can be used to prepare lead-free perovskite nanocrystals, and the controllable preparation of nanocrystals can be achieved by the template's own characteristics. This provides a new idea for us to find new functional materials of lead-free metal halide solid-state light-emitting diodes.

MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration.

Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. Our previous study has shown that MRTF-A promote the migration of MDA-MB-231 cells and WDR1 promotes breast cancer cell migration. But the exact molecular mechanism on metastasis is still not fully understood, we now report that WDR1 enhanced the effect of MRTF-A induced-MDA-MB-231 cell migration by promoting the expression of the EMT markers and migration markers via RhoA-MRTF-A signaling pathway. Importantly, WDR1 promoted the nuclear importion of MRTF-A by affecting the expression of nuclear transport protein importin. But WDR1 did not affect the expression of MRTF-A. Interestingly, MRTF-A promoted the expression of miR-206 via its promoter CArG box but miR-206 inhibits the migration of breast cancer cells through suppressing the expression of WDR1 and MRTF-A via targeted their 3'UTR. Our data thus provide important and novel insights into MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration.

Thalidomide Inhibits Adhesion Molecules in Experimental Acute Pancreatitis-Associated Lung Injury.

Preclinical Research The study evaluated the effect of thalidomide on adhesion molecule expression in acute pancreatitis-associated lung injury in rats. Acute pancreatitis was induced in rats by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct, and thalidomide (100 mg/kg) was given daily by intragastric route for 8 days before this treatment. Serum lipase (LPS), protein levels in bronchoalveolar lavage fluid (BALF), superoxide dismutase (SOD), glutathione peroxidase (GSHpx), and malondialdehyde (MDA) levels in lung were measured. Compared with the acute pancreatitis- group, lung histopathology, serum LPS, protein levels in BALF, SOD, GSHpx, and MDA levels, and the expression levels of intercellular adhesion molecule-1 and E-selectin mRNA and protein in rats given thalidomide were improved (P < 0.01). Thus, thalidomide may reduce the expression of adhesion molecules via inhibition of oxidative stress to alleviate acute pancreatitis-associated lung injury in a rat model. Drug Dev Res, 2014. © 2014 Wiley Periodicals, Inc.

A platform for preparation of monodispersed fluorescent conjugated polymer microspheres with core-shell structures.

A strategy to prepare stable monodispersed fluorescent microspheres is developed by modifying the Wessling method to synthesize poly(p-phenylenevinylene) (PPV) on the surface of a highly crosslinked polymer core. The positively charged PPV polymer precursors (pre-PPV) are adsorbed onto the core with negative charges on the surface and then the insoluble fluorescent PPVs form after thermal elimination. Each individual sphere is found to possess a very smooth surface with an even distribution of fluorescence by microscopic techniques. Very small coefficient of variance (CV) values of emission intensity (<4.0%) and size (<2.3%) are realized for microspheres prepared in the same batch. The spheres are demonstrated to have good thermal stability and photostability.

Conjugated Polyelectrolyte Containing a High Density of Pendant Phenylboronic Acid Groups for Dopamine Detection.

A fluorescent sensing system based on a conjugated polyelectrolyte was constructed to detect dopamine (DA) in complex samples. The conjugated polymer PFPE-PBA with poly[fluorenyl-alt-p-phenyleneethynylene] (PFPE) as the backbone and carrying four pendant phenylboronic acid (PBA) groups in each repeat unit was synthesized. PFPE-PBA was found to have good solubility in polar solvents. After optimization, glycine-NaOH at pH 10 was selected as the buffer, and the solvent composition of the system was set to methanol/water (9/1 by volume). Titration experiments showed that DA could effectively quench the fluorescence of the polymer solution with a response time within 60 s and a limit of detection of 23 nM. Polyols, cations, and other possible interfering substances do not significantly affect the fluorescence of the polymer, thereby allowing for the highly selective detection of DA. Furthermore, quantitative determination of DA in spiked serum and artificial urine samples was successfully demonstrated, with recoveries ranging from 96.7 to 104%. Preliminary mechanism studies suggest that the pedant PBAs capture DA via reaction with the catechol group, and the fluorescence quenching is most likely due to the photoinduced electron transfer between the aromatic part of DA and the conjugated backbone. This study provides a general strategy for the future design of conjugated polyelectrolyte-based sensing systems.

Strongly fluorescent conjugated polymer nanoparticles in aqueous colloidal solution for universal, efficient and effective development of sebaceous and blood fingerprints.

Taking the same developing strategy for different types of latent fingerprints is helpful in improving the efficiency of criminal investigation. Here we advanced a new strategy based on amino-functionalized poly(p-phenylenevinylene) nanoparticles (PPV-brPEI NPs) in aqueous colloidal solution as the developing reagent. The desirable amino functionality and strong emission of NPs were simultaneously realized by adding branched polyethyleneimine (brPEI) during the process of thermal elimination of the PPV polymer precursor. The NPs were demonstrated to have negligible effects on the extraction of biological information from DNA. Using the PPV-brPEI NPs-soaked cotton pad, both latent sebaceous fingerprints (LSFPs) and latent blood fingerprints (LBFPs) can be effectively developed on different nonporous substrates. This strategy was highly sensitive and effective for aged, contaminated and moldy fingerprints. Additionally, the developed fingerprints could tolerate humidity environment and the alcohol atmosphere. The mechanism investigation suggests that interaction between PPV-brPEI NPs and sebum ingredients contributes to the development of LSFPs and interaction between PPV-brPEI NPs and proteins in blood contributes to the development of LBFPs, but the former is not as stable as the latter. This work provides a simple, environment/operator-friendly strategy for efficient fingerprint development, which is very promising for practical criminal investigations.

Dynamic Fluorescent Anti-Counterfeiting Labels Based on Conjugated Polymers Confined in Submicron Fibrous Membranes.

Developing a new anti-counterfeiting strategy is of great significance to combating the global counterfeiting problem. Here we report the construction of a dynamic fluorescence response system for anti-counterfeiting by combining the photochromism induced by the ring-opening of spiropyran (SP) to merocyanine (MC) with the fluorescence resonance energy transfer (FRET) between the conjugated polymer and MC. After elucidating the design principle, a new conjugated polymer, PPETE-SP, consisting of a poly[p-(phenylene ethynylene)-alt-(thienylene-ethynylene)] (PPETE) backbone with pendant SP, was synthesized and characterized. With poly(methyl methacrylate) (PMMA) as the matrix, the PPETE-SP/PMMA fibrous membrane was prepared via electrospinning. Under the irradiation of UV light, the fluorescent color of the membrane dynamically changed from green to light green, then light pink, and finally pink, and this process was reversible under visible light. The fluorescence emission switch was examined for 10 cycles and proved to have good repeatability, indicating that the membrane can be directly used as an anti-counterfeiting label for multiple verifications. The FRET efficiency was found to be about 61% based on the FRET study with confocal laser scanning microscopy. The covalent bonding between PPETE backbone and SP, the confinement of PPETE-SP chains in the fibrous membrane, as well as employing PMMA as the matrix were demonstrated to be crucial in realizing the photochromism and the FRET. Different anti-counterfeiting modes were proposed, providing rich selections for operation of verification. Such facile-to-operate and hard-to-imitate dynamic fluorescent responsive materials are very promising for use in practical anti-counterfeiting applications.

[GAO Hong's clinical experience in treatment of tic disorder with acupuncture technique of cultivating the primary and regulating the mind].

The paper introduces the clinical experience of GAO Hong in treatment of tic disorder. GAO Hong believes that tic disorder results from the primary qi deficiency and mind disturbance. Acupuncture for cultivating the primary and regulating the mind is proposed specially for tic disorder. This acupuncture technique focuses on harmonizing and regulating governor vessel and conception vessel. In clinical practice, the conception vessel acupoints on the abdomen and the governor vessel acupoints on the head are selected particularly, e.g. Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6) and Guanyuan (CV 4) on the abdomen; Baihui (GV 20), Shenting (GV 24), Benshen (GB 13) and Yintang (GV 24+) on the head. The needling sequence and the insertion depth are emphasized, which affect the curative effect and GV 20 is generally punctured first. Besides, considering to the type of disorder and the affected site, tic disorder is treated in view of both syndrome/pattern differentiation and symptom differentiation.

Fluorescent Cationic Conjugated Polymer-Based Adaptive Developing Strategy for Both Sebaceous and Blood Fingerprints.

Both latent sebaceous and blood fingerprints may provide valuable information for forensic investigation. To detect both types of fingerprints with no need to predistinguish them, a new adaptive developing strategy was proposed. A cationic conjugated polymer with poly[p-(phenylene ethylene)-alt-(thienylene ethynylene)] backbone (PPETE-NMe3+) was synthesized, which was dissolved in N,N-dimethylformamide (DMF) to form the developing solution. Fingerprints were developed by a simple dropping and incubating process without any pre-/post-treatments. Fluorescent photographs of the developed fingerprints on various substrates demonstrated that this developing strategy was effective for both types of fingerprints on nonporous substrates. Gray value analysis further confirmed the enhancement of the legibility of the fingerprint images. The preliminary mechanism exploration suggested that certain weak interactions, such as hydrophobic interaction and electrostatic interaction, may synergistically contribute to the interaction between the polymer and fingerprint components. The molecular design of the polymer combined with an appropriate solvent endowed the developing system the adaptiveness toward different types of fingerprints. This adaptive developing strategy made the fingerprint-developing process more efficient and may be further extended to more practical application scenes.

Highly Stable, Nondestructive, and Simple Visualization of Latent Blood Fingerprints Based on Covalent Bonding Between the Fluorescent Conjugated Polymer and Proteins in Blood.

Latent blood fingerprints (LBFPs) can provide critical information of foul play and help identify the suspects at violent crime scenes. The current methods for LBFP visualization are still not satisfactory because of the low sensitivity or complicated protocol. This study demonstrates a simple and effective LBFP visualization strategy by integrating a new amphiphilic fluorescent amino-functionalized conjugated polymer with the cotton-pad developing protocol. LBFPs on various substrates are visualized by simply covering them with the polymer solution-soaked cotton pads. The images display clear fingerprint patterns, ridge details, and sweat pores, even on very challenging substrates such as painted wood and multicolored can. The gray value analysis confirms semiquantitatively the enhancement of the contrast between ridges and furrows. Even LBFPs with various contaminations or aged for more than 600 days are effectively developed and visualized. The developed fingerprint images show superior stability over long storage time and against solvent washing. Moreover, the polymer causes no degradation of DNAs in the blood, suggesting the possibility of further DNA profiling and identification after development. The mechanistic investigation suggests that the formation of positive or inverted images can be attributed to the synergistic effects from the affinity between polymer and blood, and the affinity betwen polymer and substrate, as well as the slight quenching of polymer fluorescence by blood. Furthermore, the covalent bonding between the protonated primary amino group and proteins in blood endows the stability of the developed fingerprints. The result rationalizes the molecular design of the fluorescent polymer and sheds new light on the future strategies to effective LBFP visualization in practical applications.

Thalidomide Reduces Activation of Murine Pancreatic Stellate Cells by Inhibiting the TGF-ß/Smad Pathway.

OBJECTIVE: The aim of this study was to investigate the effects and mechanism of thalidomide on pancreatic stellate cell (PSC) activation in mice and to find the optimal timing of thalidomide administration. METHODS: PSCs, isolated from mouse pancreas tissue, were divided into five groups with specific treatments: (A) control PSCs (PSC), (B) PSCs induced by TGF-ß1 (PSC+TGF-ß1), (C) PSCs induced by TGF-ß1 followed by thalidomide (PSC+TGF-ß1+Thalidomide), (D) PSCs receiving TGF-ß1 and thalidomide simultaneously (PSC+(TGF-ß1+Thalidomide)), and (E) PSCs treated with thalidomide only (PSC+Thalidomide). We measured the effects of thalidomide on PSC activation by detecting the expression of α-SMA, collagen type I, and the TGF-ß/Smad pathway through quantitative real-time PCR and Western blot analysis. RESULTS: Compared with TGF-ß1 alone, thalidomide significantly inhibited PSC activation by reducing α-SMA expression (P<0.05) and decreasing collagen type I deposition (P<0.05). PSCs treated with thalidomide alone showed lower expression of α-SMA and collagen type I than those treated with thalidomide and TGF-ß1 at random order (P<0.01). Thalidomide downregulated TGF-ß1 and Smad3 and upregulated Smad7 (P<0.05). CONCLUSION: Thalidomide could repress PSC activation and alleviate fibrosis by regulating the TGF-ß/Smad pathway. Preventive use of thalidomide had maximum effect, and there was no evidence for the reversal of the activation of quiescent PSCs.

Supramolecular and Physically Double-Cross-Linked Network Strategy toward Strong and Tough Elastic Fibers.

The strength and toughness are two trade-off properties of a material, yet Nature can achieve strong and tough materials by introducing sacrificial bonds into a system. Here, we present a four-component multiblock copolymer (mBCP) approach toward strong and tough elastic fibers, by introducing terpyridine moieties into poly(ether ester) mBCP elastomers. After coordination with Fe(II), supramolecular cross-links are formed within the physically cross-linked thermoplastic elastomers. The toughening elastic fibers with a double-cross-linked network structure show high tensile strength (ca. 300 MPa) and toughness (ca. 100 MJ m-3). In addition, they display excellent resilience with enhanced self-healing properties. Our strategy provides a promising way for the development of strong and tough elastomers by introducing metal-ligand sacrificial bonds into mBCPs elastomers.

Competition between energy transfer quenching and chelation enhanced fluorescence in a Cu (II) coordinated conjugated polymer system.

An investigation of the mechanism of the fluorescence quenching by Cu(2+) for a conjugated polymer system initially designed as a fluorescence "turn-on" chemosensor based on chelation enhanced fluorescence (CHEF) is described in this paper. Unlike all other metal cations tested, the polymer/Cu(2+) hybrid system with a 1:1 ratio between the receptor and Cu(2+) has only weak fluorescence with lambda(max) = 490 nm and a quantum yield of 0.004 in THF at room temperature. In solvent glasses at 77 K the fluorescence remained quenched suggesting that the quenching mechanism was due to energy transfer between the Cu(2+) and the conjugated polymer backbone. The energy transfer quenching competes effectively with the electron transfer involved in the CHEF resulting in a more selective chemosensory system.