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Find video protocols related to scientific articles indexed in Pubmed.
Choline phosphate functionalized surface: protein-resistant but cell-adhesive zwitterionic surface potential for tissue engineering.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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A choline phosphate (CP) modified surface is designed to resist protein adsorption due to its zwitterionic properties and simultaneously promote cell adhesion though its universal interaction with phosphate choline (PC) headgroups of the cell membrane. This work provides a new approach to obtain a cell-adhesive surface with a non-biofouling 'background', which has a potential for tissue engineering.
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Long-term thiol monitoring in living cells using bioorthogonal chemistry.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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Intracellular thiols play vital roles in living systems, and their in situ monitoring is of great importance. Here, we report on a bioorthogonal chemistry based fluorescent probe, which is capable of monitoring intracellular thiols in living cells for up to 36 hours with an obvious blue-to-green fluorescence change.
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[Cellular and humoral immunity in preterm infants of different gestational ages.]
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 11-20-2014
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To investigate the characteristics of immune function in newborn infants of different gestational ages.
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[Analysis of the status and countermeasures of sales supervision on medical devices].
Zhongguo Yi Liao Qi Xie Za Zhi
PUBLISHED: 10-22-2014
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This article analyzes the status quo of sales supervision on medical devices through some aspects, including the relevant regulation system, the standards of sales admittance, the supervision team and the approval of business license. According to the exiting problems, some improving countermeasures are proposed for reference.
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MMP-2 responsive polymeric micelles for cancer-targeted intracellular drug delivery.
Chem. Commun. (Camb.)
PUBLISHED: 10-21-2014
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Multifunctional Biotin-PEG-b-PLL(Mal)-peptide-DOX polymeric micelles were prepared to selectively eliminate cancer cells. The micelles were able to enhance cancer cell uptake via the receptor-mediated endocytosis and respond to the stimulus of cancer cell excessive secreted protease MMP-2 to release the anticancer drug and induce apoptosis of cancer cells in a targeted manner.
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[Primary exploration of the product quality supervision on medical devices in use].
Zhongguo Yi Liao Qi Xie Za Zhi
PUBLISHED: 09-23-2014
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This paper focuses on issues needed to be clear towards the product quality supervision of medical devices in use. The life circle of medical devices, the supervision regarding its boundary, target, emphasis, basis and standards have been analyzed in turn. A clear and creative idea is also provided for theoretical exploration of the supervision on medical devices in use.
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Ebola virus disease: potential use of melatonin as a treatment.
J. Pineal Res.
PUBLISHED: 09-22-2014
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The purpose of this report is to emphasize the potential utility for the use of melatonin in the treatment of individuals who are infected with the Ebola virus. The pathological changes associated with an Ebola infection include, most notably, endothelial disruption, disseminated intravascular coagulation and multiple organ hemorrhage. Melatonin has been shown to target these alterations. Numerous similarities between Ebola virus infection and septic shock have been recognized for more than a decade. Moreover, melatonin has been successfully employed for the treatment of sepsis in many experimental and clinical studies. Based on these factors, as the number of treatments currently available is limited and the useable products are not abundant, the use of melatonin for the treatment of Ebola virus infection is encouraged. Additionally, melatonin has a high safety profile, is readily available and can be orally self-administered; thus, the use of melatonin is compatible with the large scale of this serious outbreak.
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INDOLE-3-ACETIC ACID INDUCIBLE 17 positively modulates natural leaf senescence through melatonin-mediated pathway in Arabidopsis.
J. Pineal Res.
PUBLISHED: 09-02-2014
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Melatonin (N-acetyl-5-methoxytryptamine) functions as a ubiquitous modulator in multiple plant developmental processes and various stress responses. However, the involvement of melatonin in natural leaf senescence and the underlying molecular mechanism in Arabidopsis remain unclear. In this study, we found that the endogenous melatonin level was significantly induced in a developmental stage-dependent manner, and exogenous melatonin treatment delayed natural leaf senescence in Arabidopsis. The expression level of AUXIN RESISTANT 3 (AXR3)/INDOLE-3-ACETIC ACID INDUCIBLE 17 (IAA17) was significantly downregulated by exogenous melatonin treatment and decreased with developmental age in Arabidopsis. Further investigation indicated that AtIAA17-overexpressing plants showed early leaf senescence with lower chlorophyll content in rosette leaves compared with wild-type plants, while AtIAA17 knockout mutants displayed delayed leaf senescence with higher chlorophyll content. Notably, exogenous melatonin-delayed leaf senescence was largely alleviated in AtIAA17-overexpressing plants, and AtIAA17-activated senescence-related SENESCENCE 4 (SEN4) and SENESCENCE-ASSOCIATED GENE 12 (SAG12) transcripts might have contributed to the process of natural leaf senescence. Taken together, the results indicate that AtIAA17 is a positive modulator of natural leaf senescence and provides direct link between melatonin and AtIAA17 in the process of natural leaf senescence in Arabidopsis.
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A pH-responsive prodrug for real-time drug release monitoring and targeted cancer therapy.
Chem. Commun. (Camb.)
PUBLISHED: 08-23-2014
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A novel cancer targeting and pH-responsive prodrug was successfully designed and synthesized. This M-prodrug was demonstrated to have real-time drug release monitoring capability based on the concept of contact-mediated quenching between doxorubicin and a coumarin derivative.
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[Efficacy of inhaled nitric oxide in premature infants with hypoxic respiratory failure].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 08-21-2014
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To investigate the safety and efficacy of low-concentration inhaled nitric oxide (NO) in the treatment of hypoxic respiratory failure (HRF) among premature infants.
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Stepwise-acid-active multifunctional mesoporous silica nanoparticles for tumor-specific nucleus-targeted drug delivery.
ACS Appl Mater Interfaces
PUBLISHED: 08-18-2014
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In this paper, a novel stepwise-acid-active multifunctional mesoporous silica nanoparticle (MSN-(SA)TAT&(DMA)K11) was developed as a drug carrier. The MSN-(SA)TAT&(DMA)K11 is able to reverse its surface charge from negative to positive in the mildly acidic tumor extracellular environment. Then, the fast endo/lysosomal escape and subsequent nucleus targeting as well as intranuclear drug release can be realized after cellular internalization. Because of the difference in acidity between the tumor extracellular environment and that of endo/lysosomes, this multifunctional MSN-(SA)TAT&(DMA)K11 exhibits a stepwise-acid-active drug delivery with a tumor-specific nucleus-targeted property.
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Effects of Melatonin on the Proliferation and Apoptosis of Sheep Granulosa Cells under Thermal Stress.
Int J Mol Sci
PUBLISHED: 07-30-2014
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The cross-talk between oocyte and somatic cells plays a crucial role in the regulation of follicular development and oocyte maturation. As a result, granulosa cell apoptosis causes follicular atresia. In this study, sheep granulosa cells were cultured under thermal stress to induce apoptosis, and melatonin (MT) was examined to evaluate its potential effects on heat-induced granulosa cell injury. The results demonstrated that the Colony Forming Efficiency (CFE) of granulosa cells was significantly decreased (heat 19.70% ± 1.29% vs. control 26.96% ± 1.81%, p < 0.05) and the apoptosis rate was significantly increased (heat 56.16% ± 13.95% vs. control 22.80% ± 12.16%, p < 0.05) in granulosa cells with thermal stress compared with the control group. Melatonin (10-7 M) remarkably reduced the negative effects caused by thermal stress in the granulosa cells. This reduction was indicated by the improved CFE and decreased apoptotic rate of these cells. The beneficial effects of melatonin on thermal stressed granulosa cells were not inhibited by its membrane receptor antagonist luzindole. A mechanistic exploration indicated that melatonin (10-7 M) down-regulated p53 and up-regulated Bcl-2 and LHR gene expression of granulosa cells under thermal stress. This study provides evidence for the molecular mechanisms of the protective effects of melatonin on granulosa cells during thermal stress.
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Fundamental issues related to the origin of melatonin and melatonin isomers during evolution: relation to their biological functions.
Int J Mol Sci
PUBLISHED: 07-11-2014
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Melatonin and melatonin isomers exist and/or coexist in living organisms including yeasts, bacteria and plants. The levels of melatonin isomers are significantly higher than that of melatonin in some plants and in several fermented products such as in wine and bread. Currently, there are no reports documenting the presence of melatonin isomers in vertebrates. From an evolutionary point of view, it is unlikely that melatonin isomers do not exist in vertebrates. On the other hand, large quantities of the microbial flora exist in the gut of the vertebrates. These microorganisms frequently exchange materials with the host. Melatonin isomers, which are produced by these organisms inevitably enter the host's system. The origins of melatonin and its isomers can be traced back to photosynthetic bacteria and other primitive unicellular organisms. Since some of these bacteria are believed to be the precursors of mitochondria and chloroplasts these cellular organelles may be the primary sites of melatonin production in animals or in plants, respectively. Phylogenic analysis based on its rate-limiting synthetic enzyme, serotonin N-acetyltransferase (SNAT), indicates its multiple origins during evolution. Therefore, it is likely that melatonin and its isomer are also present in the domain of archaea, which perhaps require these molecules to protect them against hostile environments including extremely high or low temperature. Evidence indicates that the initial and primary function of melatonin and its isomers was to serve as the first-line of defence against oxidative stress and all other functions were acquired during evolution either by the process of adoption or by the extension of its antioxidative capacity.
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Inhibiting effect of electroacupuncture at zusanli on early inflammatory factor levels formed by postoperative abdominal adhesions.
Evid Based Complement Alternat Med
PUBLISHED: 07-07-2014
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We observed the inhibitive effect of electroacupuncture (EA) at Zusanli on inflammatory mediators of postoperative intra-abdominal adhesions to find out the relationship between EA and the cholinergic anti-inflammatory pathway. Sixty-four rats were divided into 8 groups (A-H, each = 8): A = sham control; B = abdominal adhesions model; C = abdominal adhesions plus EA; D = sham acupoint control; E = abdominal adhesions plus vagotomy; F = abdominal adhesions plus EA after vagotomy; G = abdominal adhesions plus ?-bungarotoxin (BGT); and H = abdominal adhesions plus EA after ?-BGT. ?-BGT (1??g/kg) was injected into the abdominal cavity after surgery, and the bilateral celiac vagotomy was done during the surgery. On the third day the levels of inflammatory mediators (TNF-?, nitric oxide (NO), and nitric oxide synthase (NOS)) in tissues were evaluated. The abdominal adhesion groups developed obvious edema. Compared with sham control, the abdominal adhesion resulted in a significant elevation of inflammatory mediators. EA lowered the elevated levels of inflammatory mediators significantly; EA plus ?-BGT and vagotomy showed less anti-inflammatory effects. The activation of the cholinergic anti-inflammatory pathway might be one of the mechanisms of EA at Zusanli acupoints to exert the anti-inflammatory effects.
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Cancer-targeted functional gold nanoparticles for apoptosis induction and real-time imaging based on FRET.
Nanoscale
PUBLISHED: 07-04-2014
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A versatile gold nanoparticle-based multifunctional RB-DEVD-AuNP-DTP has been developed to induce the targeted apoptosis of cancer cells and image in real time the progress of the apoptosis. The multifunctional nanoparticles were demonstrated to have the ability to initiate mitochondria-dependent apoptosis and activate caspase-3 for real-time imaging of the progression of apoptosis.
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High length-diameter ratio nanotubes self-assembled from a facial cyclopeptide.
Soft Matter
PUBLISHED: 07-02-2014
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A six-residue facial cyclopeptide was designed with the following sequence: c-[D-Leu-L-Lys-D-Ala-L-Lys-D-Leu-L-Gln] (CP). Extensive hydrogen bonding between the cyclopeptide backbones mainly regulated CP to self-assemble into single-walled nanotubes. Simultaneously, the hydrophobic interaction among facial hydrophobic side chains of CP was introduced to stabilize the hydrogen bonding, resulting in the formation of the thick-walled nanotubes with high length–diameter ratios.
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Postconditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury involving mitochondrial ATP-dependent potassium channel and mitochondrial permeability transition pore.
Neurol. Res.
PUBLISHED: 06-25-2014
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Postconditioning with sevoflurane has been shown to protect against focal cerebral ischemia and reperfusion injury. However, the mechanism remains elusive. In this study, we tested the hypothesis that mitochondrial ATP-sensitive potassium (mitoKATP) and mitochondrial permeability transition pore (mPTP) play roles in the neuroprotection of postconditioning with sevoflurane.
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Melatonin promotes superovulation in sika deer (Cervus nippon).
Int J Mol Sci
PUBLISHED: 05-21-2014
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In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1±2.04 ng/mL) at the point of insemination, compared with the baseline levels (4.98±0.07 ng/mL) in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p<0.05). The average number of embryos in the deer treated with 40 mg of melatonin was higher than that of the control; however, this increase did not reach significant difference (p>0.05), which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed.
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Melatonin identified in meats and other food stuffs: potentially nutritional impact.
J. Pineal Res.
PUBLISHED: 05-14-2014
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Melatonin has been identified in primitive photosynthetic bacteria, fungi, plants, and animals including humans. Vegetables, fruits, cereals, wine, and beers all contain melatonin. However, the melatonin content in meats has not been reported previously. Here, for the first time, we report melatonin in meats, eggs, colostrum, and in other edible food products. The levels of melatonin measured by HPLC, in lamb, beef, pork, chicken, and fish, are comparable to other food stuffs (in the range of ng/g). These levels are significantly higher than melatonin concentrations in the blood of vertebrates. As melatonin is a potent antioxidant, its presence in the meat could contribute to shelf life duration as well as preserve their quality and taste. In addition, the consumption of these foods by humans or animals could have health benefits considering the important functions of melatonin as a potent free radical scavenger and antioxidant.
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Multifunctional Enveloped Mesoporous Silica Nanoparticles for Subcellular Co-delivery of Drug and Therapeutic Peptide.
Sci Rep
PUBLISHED: 04-30-2014
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A multifunctional enveloped nanodevice based on mesoporous silica nanoparticle (MSN) was delicately designed for subcellular co-delivery of drug and therapeutic peptide to tumor cells. Mesoporous silica MCM-41 nanoparticles were used as the core for loading antineoplastic drug topotecan (TPT). The surface of nanoparticles was decorated with mitochondria-targeted therapeutic agent (Tpep) containing triphenylphosphonium (TPP) and antibiotic peptide (KLAKLAK)2 via disulfide linkage, followed by coating with a charge reversal polyanion poly(ethylene glycol)-blocked-2,3-dimethylmaleic anhydride-modified poly(L-lysine) (PEG-PLL(DMA)) via electrostatic interaction. It was found that the outer shielding layer could be removed at acidic tumor microenvironment due to the degradation of DMA blocks and the cellular uptake was significantly enhanced by the formation of cationic nanoparticles. After endocytosis, due to the cleavage of disulfide bonds in the presence of intracellular glutathione (GSH), pharmacological agents (Tpep and TPT) could be released from the nanoparticles and subsequently induce specific damage of tumor cell mitochondria and nucleus respectively with remarkable synergistic antitumor effect.
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Electroacupuncture at Zusanli (ST36) promotes gastric emptying and mucosal blood flow during oral resuscitation of scalded rats with a pyruvate-enriched ORS.
Burns
PUBLISHED: 04-02-2014
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The aim of this study was to investigate the effect of electroacupuncture at ST36 (EA ST36) on gastric emptying and mucosal blood flow during intragastric resuscitation with pyruvate-enriched oral rehydration solution (Pyr-ORS) in scalded rats.
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Effect of salidroside on lung injury by upregulating peroxisome proliferator-activated receptor ? expression in septic rats.
Exp Ther Med
PUBLISHED: 03-11-2014
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Successful drug treatment for sepsis-related acute lung injury (ALI) remains a major clinical problem. Thus, the aim of the present study was to investigate the beneficial effects of salidroside on ameliorating cecal ligation and puncture (CLP)-induced lung inflammation. Rats underwent CLP surgery to induce ALI and 800 mg/kg salidroside (i.v.) was administered 24 h after the CLP challenge. Subsequently, biochemical changes in the blood and lung tissues, as well as morphological and histological alterations in the lungs, that were associated with inflammation and injury were analysed. CLP was shown to significantly increase the serum levels of plasma tumour necrosis factor-? and interleukin-6, -1? and-10. In addition, CLP increased pulmonary oedema, thickened the alveolar septa and caused inflammation in the lung cells. These changes were ameliorated by the administration of 800 mg/kg salidroside (i.v.) 24 h after the CLP challenge. This post-treatment drug administration also significantly attenuated the lipopolysaccharide-induced activation of nuclear factor-?? and increased the release of peroxisome proliferator-activated receptor ? in the lung tissue. Therefore, salidroside administered following the induction of ALI by CLP significantly prevented and reversed lung tissue injuries. The positive post-treatment effects of salidroside administration indicated that salidroside may be a potential candidate for the management of lung inflammation in CLP-induced endotoxemia and septic shock.
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Effect of melilotus extract on lung injury by upregulating the expression of cannabinoid CB2 receptors in septic rats.
BMC Complement Altern Med
PUBLISHED: 02-24-2014
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M. Suaveolens Ledeb has long been used in China to treat inflammatory infectious diseases. Melilotus is extracted from Melilotus Suaveolens Ledeb and its therapeutic potential is associated with its anti-inflammatory activity. However, the precise mechanisms underlying its effects are unknown. This study was conducted to evaluate the protective effects of melilotus extract in a rat cecal ligation and puncture (CLP)-induced animal model of acute lung injury (ALI).
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Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review.
J. Pineal Res.
PUBLISHED: 02-19-2014
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Free radicals generated within subcellular compartments damage macromolecules which lead to severe structural changes and functional alterations of cellular organelles. A manifestation of free radical injury to biological membranes is the process of lipid peroxidation, an autooxidative chain reaction in which polyunsaturated fatty acids in the membrane are the substrate. There is considerable evidence that damage to polyunsaturated fatty acids tends to reduce membrane fluidity. However, adequate levels of fluidity are essential for the proper functioning of biological membranes. Thus, there is considerable interest in antioxidant molecules which are able to stabilize membranes because of their protective effects against lipid peroxidation. Melatonin is an indoleamine that modulates a wide variety of endocrine, neural and immune functions. Over the last two decades, intensive research has proven this molecule, as well as its metabolites, to possess substantial antioxidant activity. In addition to their ability to scavenge several reactive oxygen and nitrogen species, melatonin increases the activity of the glutathione redox enzymes, that is, glutathione peroxidase and reductase, as well as other antioxidant enzymes. These beneficial effects of melatonin are more significant because of its small molecular size and its amphipathic behaviour, which facilitates ease of melatonin penetration into every subcellular compartment. In the present work, we review the current information related to the beneficial effects of melatonin in maintaining the fluidity of biological membranes against free radical attack, and further, we discuss its implications for ageing and disease.
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Effect of Melilotus extract on lung injury via the upregulation of tumor necrosis factor-?-induced protein-8-like 2 in septic mice.
Mol Med Rep
PUBLISHED: 02-06-2014
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As a Traditional Chinese Medicine, Melilotus extracts have been reported to function as an anti?inflammatory agent, antioxidant and inhibitor of capillary permeability. The present study aimed to identify the mechanisms by which Melilotus interferes with inflammation?associated and oxidative stress pathways during sepsis. An animal model of cecal ligation?perforation (CLP)?induced sepsis was established. Two hours prior to surgery, animals in the treatment group were administered 25 mg/kg Melilotus extract tablets and subsequently every 8 h. At 24 h post?administration, pathological modifications in lung tissue and expression levels of tumor necrosis factor???induced protein?8?like 2 (TIPE2) expression, nuclear factor (NF)??B, toll?like receptor 4 (TLR4), heme oxygenase?1 (HO?1), inhibitor of ?B kinase (I?B), pro?inflammatory mediators (interleukin?6 and tumor necrosis factor??), myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), were examined. The results showed that Melilotus extract had a marked effect on the pathological manifestation of lung tissue and lung inflammatory response, the upregulation of TIPE2, HO?1 and I?B expression, and the inhibition of TLR4 and NF??B activities. In addition, following treatment with Melilotus extract, the model animals demonstrated decreased levels of MPO and MDA as well as increased levels of SOD. In conclusion, these results indicated that Melilotus extract may be a potential therapeutic agent for the treatment of CLP?induced lung injury, the mechanism of which proceeded via inflammation? and oxidation?associated pathways by increasing TIPE2 expression.
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Can tongue acupuncture enhance body acupuncture? First results from heart rate variability and clinical scores in patients with depression.
Evid Based Complement Alternat Med
PUBLISHED: 02-04-2014
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Tongue acupuncture (TA) is a method which is not used in western medicine and even in China it is applied very rarely in clinical practice. This study aimed at investigating whether additional TA can improve the efficacy of body acupuncture (BA) in patients with depression. Twenty patients with a mean age of?±?SD of 42.9 ± 11.2 years were randomly divided into two groups (n = 10 patients each), one group receiving BA (Zusanli, Sanyinjiao, Neiguan, Shenting, Yintang, and Baihui) and the other receiving BA and TA (Liver, Heart, and Brain). The quantitative and qualitative outcome measures were heart rate (HR), heart rate variability (HRV), and different clinical scores. We found that in both groups all scores and HR improved significantly, whereas HRV increased partly significantly. It seems that TA can enhance acute and treatment effects of BA in patients with depression. The investigation of de qi sensation in TA needs further attention.
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A pH-responsive drug nanovehicle constructed by reversible attachment of cholesterol to PEGylated poly(l-lysine) via catechol-boronic acid ester formation.
Acta Biomater
PUBLISHED: 01-29-2014
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The present work reports the construction of a drug delivery nanovehicle via a pH-sensitive assembly strategy for improved cellular internalization and intracellular drug liberation. Through spontaneous formation of boronate linkage in physiological conditions, phenylboronic acid-modified cholesterol was able to attach onto catechol-pending methoxypoly(ethylene glycol)-block-poly(l-lysine). This comb-type polymer can self-organize into a micellar nanoconstruction that is able to effectively encapsulate poorly water-soluble agents. The blank micelles exhibited negligible in vitro cytotoxicity, yet doxorubicin (DOX)-loaded micelles could effectively induce cell death at a level comparable to free DOX. Owing to the acid-labile feature of the boronate linkage, a reduction in environmental pH from pH 7.4 to 5.0 could trigger the dissociation of the nanoconstruction, which in turn could accelerate the liberation of entrapped drugs. Importantly, the blockage of endosomal acidification in HeLa cells by NH4Cl treatment significantly decreased the nuclear uptake efficiency and cell-killing effect mediated by the DOX-loaded nanoassembly, suggesting that acid-triggered destruction of the nanoconstruction is of significant importance in enhanced drug efficacy. Moreover, confocal fluorescence microscopy and flow cytometry assay revealed the effective internalization of the nanoassemblies, and their cellular uptake exhibited a cholesterol dose-dependent profile, indicating the contribution of introduced cholesterol functionality to the transmembrane process of the nanoassembly.
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Extrapineal melatonin: sources, regulation, and potential functions.
Cell. Mol. Life Sci.
PUBLISHED: 01-27-2014
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Endogenous melatonin is synthesized from tryptophan via 5-hydroxytryptamine. It is considered an indoleamine from a biochemical point of view because the melatonin molecule contains a substituted indolic ring with an amino group. The circadian production of melatonin by the pineal gland explains its chronobiotic influence on organismal activity, including the endocrine and non-endocrine rhythms. Other functions of melatonin, including its antioxidant and anti-inflammatory properties, its genomic effects, and its capacity to modulate mitochondrial homeostasis, are linked to the redox status of cells and tissues. With the aid of specific melatonin antibodies, the presence of melatonin has been detected in multiple extrapineal tissues including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. In most of these tissues, the melatonin-synthesizing enzymes have been identified. Melatonin is present in essentially all biological fluids including cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk. In several of these fluids, melatonin concentrations exceed those in the blood. The importance of the continual availability of melatonin at the cellular level is important for its physiological regulation of cell homeostasis, and may be relevant to its therapeutic applications. Because of this, it is essential to compile information related to its peripheral production and regulation of this ubiquitously acting indoleamine. Thus, this review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids of mammals including humans.
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A boronate-linked linear-hyperbranched polymeric nanovehicle for pH-dependent tumor-targeted drug delivery.
Biomaterials
PUBLISHED: 01-21-2014
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Advanced drug delivery systems, which possess post-functionalization feasibility to achieve targetability and traceability, favorable pharmacokinetics with dynamic but controllable stability, and preferable tumor accumulation with prolonged drug residence in disease sites, represent ideal nanomedicine paradigm for tumor therapy. To address this challenge, here we reported a dynamic module-assembly strategy based on reversible boronic acid/1,3-diol bioorthogonality. As a prototype, metastable hybrid nanoself-assembly between hydrophobic hyperbranched diol-enriched polycarbonate (HP-OH) and hydrophilic linear PEG terminated with phenylboronic acid (mPEG-PBA) is demonstrated in vitro and in vivo. The nanoconstruction maintained excellent stability with little leakage of loaded drugs under the simulated physiological conditions. Such a stable nanostructure enabled the effective in vivo tumor accumulation in tumor site as revealed by NIR imaging technique. More importantly, this nanoconstruction presented a pH-labile destruction profile in response to acidic microenvironment and simultaneously the fast liberation of loaded drugs. Accordingly at the cellular level, the intracellular structural dissociation was also proved in terms of the strong acidity in late endosome/lysosome, thus favoring the prolonged retention of remaining drug-loaded HP-OH aggregates within tumor cells. Hence, our delicate design open up a dynamical module-assembly path to develop site and time dual-controlled nanotherapeutics for tumor chemotherapy, allowing enhanced tumor selectivity through prolonged retention of delivery system in tumor cells followed by a timely drug release pattern.
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Expression of Bcl-2 and NF-?B in brain tissue after acute renal ischemia-reperfusion in rats.
Asian Pac J Trop Med
PUBLISHED: 01-15-2014
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To investigate the effect of acute renal ischemia reperfusion on brain tissue.
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Role of melatonin on production and preservation of gametes and embryos: a brief review.
Anim. Reprod. Sci.
PUBLISHED: 01-15-2014
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The aim of this brief review is to clarify the role of melatonin in the production and preservation of mammalian gametes and embryos. Melatonin is an indoleamine synthesized from tryptophan in the pineal gland and other organs that operates as a hypothalamic-pituitary-gonadal axis modulator and regulates the waxing and waning of seasonal reproductive competence in photoperiodic mammals. A major function of the melatonin rhythm is to transmit information about the length of the daily photoperiod to the circadian and circannual systems in order to provide time-of-day and time-of-year information, respectively, to the organism. Melatonin is also a powerful antioxidant and anti-apoptotic agent, which is due to its direct scavenging of toxic oxygen derivatives and its ability to reduce the formation of reactive species. Mammalian gametes and embryos are highly vulnerable to oxidative stress due to the presence of high lipid levels; during artificial breeding procedures, these structures are exposed to dramatic changes in the microenvironment, which have a direct bearing on their function and viability. Free radicals influence the balance between oxidation-reduction reactions, disturb the transbilayer-phospholipid asymmetry of the plasma membrane and enhance lipid peroxidation. Melatonin, due to its amphiphilic nature, is undoubtedly useful in tissues by protecting them from free radical-mediated oxidative damage and cellular death. The supplementation of melatonin to semen extender or culture medium significantly improves sperm viability, oocyte competence and blastocyst development in vitro.
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A FRET-Based Dual-Targeting Theranostic Chimeric Peptide for Tumor Therapy and Real-time Apoptosis Imaging.
Adv Healthc Mater
PUBLISHED: 01-09-2014
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A FRET-based chimeric peptide is reported to mediate specific tumor cell uptaking and apoptosis. Importantly, this chimeric peptide is fluorescence quenched (OFF). Once the apoptosis is initiated and propagated, green fluorescence is lighted up rapidly (ON), achieving simultaneous tumor therapy and real-time apoptosis monitoring.
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Atorvastatin increases lipopolysaccharide-induced expression of tumour necrosis factor-?-induced protein 8-like 2 in RAW264.7 cells.
Exp Ther Med
PUBLISHED: 01-04-2014
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RAW264.7 cells are one of the major sources of productive inflammatory biomediators, including tumour necrosis factor-? (TNF-?) and interleukin (IL)-6. TNF-?-induced protein 8-like 2 (TIPE2) is an essential negative regulator of Toll-like and T-cell receptors, and the selective expression in the immune system prevents hyper-responsiveness and maintains immune homeostasis. The aim of the present study was to investigate whether atorvastatin upregulates the expression of TIPE2 and further regulates the inflammatory response and oxidation emergency response in RAW264.7 cells. RAW264.7 cells were incubated in Dulbecco's modified Eagle's medium containing lipopolysaccharide (LPS) in the presence or absence of atorvastatin. Following incubation, the medium was collected and the levels of TNF-? and IL-6 were measured using an enzyme-linked immunosorbent assay. The cells were harvested, and the mRNA and protein expression levels of TIPE2, macrophage migration inhibitory factor (MIF), I?B and nuclear factor (NF-?B)-?B were analysed using quantitative polymerase chain reaction and western blotting analysis, respectively, the expression of NOS, COX-2 and HO-1 protein were essayed by western blotting analysis, NO and ROS activities were determined. The results revealed that LPS increased the mRNA and protein expression levels of TIPE2, MIF and NF-?B, as well as the production of IL-6 and TNF-?, in a dose and time dependent manner in RAW264.7 cells. Meanwhile, LPS enhanced the expression of NOS and COX-2 protein, blocked HO-1 protein expression, increased NO and PGE2 production and ROS activity in a dose dependent manner in RAW264.7 cells. Atorvastatin significantly increased LPS induced expression of TIPE2, downregulated the expression of NOS, COX-2, MIF and NF-?B and the production of PGE2, NO, IL-6 and TNF-? in a time and dose dependent manner, and increased HO-1 protein expression, reduced ROS production in a dose dependent manner. The observations indicated that atorvastatin upregulated LPS induced expression of TIPE2 and consequently inhibited MIF, NF-?B, NOS and COX-2 expression and the production of NO, PGE2, TNF-? and IL-6, increased HO-1 expression, and inhibited ROS activity in cultured RAW264.7 cells.
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Melatonin enhances photo-oxidation of 2',7'-dichlorodihydrofluorescein by an antioxidant reaction that renders N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK).
PLoS ONE
PUBLISHED: 01-01-2014
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The indolamine melatonin (MEL) is described as an antioxidant and a free radical scavenger. However occasionally, the indoleamine has been reported to increase free radicals with insufficient mechanistic explanation. In an attempt to find a reason for those controversial results, a potential mechanism that explains MEL prooxidant activity is investigated. The current controversy about redox detection methods has prompted us to search a possible interaction between MEL and dichlorodihydrofluorescein (DCFH2), perhaps the most widely fluorescence probe employed for free radicals detection in cellular models. Here, it is demonstrated that melatonin potentiates the photooxidation of DCFH2 in a cell-free system, increasing the production of its fluorescent metabolite. Indeed, MEL works as an antioxidant scavenging hydroxyl radicals in this system. Thus, this reaction between MEL and DCFH2 produces N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), a biogenic amine with antioxidant properties too. This reaction is O2 and light dependent and it is prevented by antioxidants such as N-acetylcysteine or ascorbic acid. Furthermore, when DCFH2 has been employed to evaluate antioxidant or prooxidant activities of MEL in cellular models it is confirmed that it works as an antioxidant but these results can be modulated by light misleading to a prooxidant conclusion. In conclusion, here is demonstrated that DCFH2, light and melatonin interact and results obtained using these fluorescence probes in studies with melatonin have to be carefully interpreted.
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Multi-Functional Envelope-Type Nanoparticles Assembled from Amphiphilic Peptidic Prodrug with Improved Anti-Tumor Activity.
ACS Appl Mater Interfaces
PUBLISHED: 12-20-2013
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A novel multifunctional amphiphilic peptidic prodrug was reported here by conjugating the antitumor drug of doxorubicin (DOX) to the hydrophobic tail of a designed peptide-amphiphile (PA), in which the hydrophilic peptide headgroup comprises a glycine-arginine-glycine-aspartic acid-serine (GRGDS) sequence and octaarginine (R8) sequence. Because of the amphiphilic nature, this peptidic prodrug can spontaneously self-assemble into spherical multifunctional envelop-type nanoparticles (MENPs) with the functional peptide sequences gathered on surface. By means of the multifunctions of RGD-mediated tumor targeting, R8-mediated membrane penetration and intracellular protease-mediated hydrolyzing peptide bonds, the MENPs could targeted deliver doxorubicin (DOX) to tumor cells, showing improved antitumor activity both in vitro and in vivo with much reduced side effects.
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Clinical relevance of melatonin in ovarian and placental physiology: a review.
Gynecol. Endocrinol.
PUBLISHED: 12-09-2013
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Abstract Within the last decade, the synthesis of melatonin in and its functions at the level of the peripheral reproductive organs has come into better focus. Melatonin is produced at several reproductive organ sites, e.g., the oocyte, ovarian follicular cells and the placental cytotrophoblasts. Moreover, these cells also contain membrane receptors for this indoleamine. In addition, via the free radical scavenging activity of melatonin and its metabolites, oxidative stress is reduced in all reproductive organ cells ensuring their optimal function. Enhancement of oocyte maturation and preservation of oocyte quality may be major functions of melatonin. Oocyte damage reduces successful fertilization and the development of a healthy fetus. The findings that melatonin protects the oocyte from toxic oxygen species have implications for improving the outcome of in vitro fertilization-embryo transfer procedures, as already shown in two published reports. Some actions of melatonin in the placenta may be context specific. Thus, melatonin is believed to function in the maintenance of optimal placental homeostasis by deferring apoptosis of villous cytotrophoblasts, while protecting syncytiotrophoblasts from oxidative damage. Melatonin reduces oxidative damage in the placenta and may improve hemodynamics and nutrient transfer at the placental-uterine interface. The use of melatonin to treat preeclampsia should also be considered.
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[Controlled research on multiple sclerosis treated with electroacupuncture and acupoint injection].
Zhongguo Zhen Jiu
PUBLISHED: 12-05-2013
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To observe the clinical efficacy of multiple sclerosis (MS) treated with electroacupuncture and acupoint injection.
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A coumarin derivative as a fluorogenic glycoproteomic probe for biological imaging.
Chem. Commun. (Camb.)
PUBLISHED: 11-26-2013
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Fluorescence imaging in living cells is typically carried out using a functionalized fluorescent dye. But it often causes strong background noise under many conditions where washing is not applicable. Here, we report on a coumarin based fluorogenic probe, which can be used as a bioorthogonal-labeling tool for glycoproteins. The results indicated that the probe was able to image glycoproteins in living cells and it may also be suitable for intracellular imaging.
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Dual-Targeting Pro-apoptotic Peptide for Programmed Cancer Cell Death via Specific Mitochondria Damage.
Sci Rep
PUBLISHED: 09-17-2013
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Mitochondria are vital organelles to eukaryotic cells. Damage to mitochondria will cause irreversible cell death or apoptosis. In this report, we aim at programmed cancer cell death via specific mitochondrial damage. Herein, a functionalized pro-apoptotic peptide demonstrates a dual-targeting capability using folic acid (FA) (targeting agent I) and triphenylphosphonium (TPP) cation (targeting agent II). FA is a cancer-targeting agent, which can increase the cellular uptake of the pro-apoptotic peptide via receptor-mediated endocytosis. And the TPP cation is the mitochondrial targeting agent, which specifically delivers the pro-apoptotic peptide to its particular subcellular mitochondria after internalized by cancer cells. Then the pro-apoptotic peptide accumulates in mitochondria and causes its serious damage. This dual-targeting strategy has the potential to effectively transport the pro-apoptotic peptide to targeted cancer cell mitochondria, inducing mitochondrial dysfunction and triggering the mitochondria-dependent apoptosis to efficiently eliminate cancer cells.
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Fabrication of Novel Reduction-Sensitive Gene Vectors Based on Three-Armed Peptides.
Macromol Biosci
PUBLISHED: 09-16-2013
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To address the inherent barriers of gene transfection, two reduction-sensitive branched polypeptides (RBPs) are synthesized and explored as novel non-viral gene vectors. The introduced disulfide linkages in RBPs facilitate glutathione-triggered intracellular gene release and reduce polymer degradation-induced cytotoxicity. Furthermore, the highly branched architecture concurrently realizes multivalency for strong DNA binding and elicits conformational flexibility for tight DNA compacting, which are beneficial for cellular entry. To increase the endosomal escape of plasmid DNA, pH-sensitive histidyl residues are incorporated into RBPs to improve buffer capacity in an acidic environment. In vitro study demonstrates that RBPs can efficiently mediate the DNA transfection and avoid apparent cytotoxicity in HeLa and COS7. The present gene delivery system offers a simple and flexible approach to fabricate microenvironment-specific branched gene vectors for gene therapy.
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Continuous auricular electroacupuncture can significantly improve heart rate variability and clinical scores in patients with depression: first results from a transcontinental study.
Evid Based Complement Alternat Med
PUBLISHED: 09-13-2013
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The goal of this study was to investigate the impact and acceptability of providing continuous auricular electroacupuncture as an adjunct to conventional medications for patients with depression. Ten patients with a mean age ± SD of 43.3 ± 10.4 years were able to provide informed consent. The quantitative and qualitative outcome measures were heart rate, heart rate variability (HRV), and different clinical scores. The study documented that a special kind of auricular electro acupuncture, applied over a period of three days, can improve various aspects of quality of life significantly but also highlighted the significant increase of HRV whilst having acupuncture treatment. In conclusion, our study shows stimulation-related and quantifiable clinical and physiological alterations in parameters after continuous auricular acupoint stimulation in patients with depression. Improved access to electro acupuncture treatment would be of major benefit for these patients. Further studies are necessary in order to verify the gained results.
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Acidity-Promoted Cellular Uptake and Drug Release Mediated by Amine-Functionalized Block Polycarbonates Prepared via One-Shot Ring-Opening Copolymerization.
Macromol Biosci
PUBLISHED: 09-09-2013
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This paper reports a drug nanovehicle self-assembled from an amine-functionalized block copolymer poly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione)-block-poly(1,3-dioxepan-2-one) (PADMC-b-PTeMC), which is prepared by controlable ring-opening block copolymerization attractively in a "one-shot feeding" pathway. The copolymers display high cell-biocompatibility with no apparent cytotoxicities detected in 293T and HeLa cells. Due to their amphiphilic nature, PADMC-b-PTeMC copolymers can self-assemble into nanosized micelles capable of loading anticancer drugs such as camptothecin (CPT) and doxorubicin (DOX). In particular, the outer PADMC shell endows the PADMC-b-PTeMC nanomicelles with pH-dependent control over the micellar morphology, cell uptake efficiency, and the drug release pattern. Confocal inspection reveals the remarkably enhanced cellular internalization of drug loaded micelles by cancerous HeLa cells at relatively lower pH 5.8 simulating the mildly acid microenvironment in tumors. Along with the acidity-triggered volume expansion of micelles, an accelerated CPT release in vitro occurs. The obtained results adumbrate the possibility of completely biodegradable PADMC-b-PTeMC as pH-sensitive drug carriers for tumor chemotherapy.
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Identification of genes for melatonin synthetic enzymes in Red Fuji apple (Malus domestica Borkh.cv.Red) and their expression and melatonin production during fruit development.
J. Pineal Res.
PUBLISHED: 08-22-2013
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Melatonin is present in many edible fruits; however, the presence of melatonin in apple has not previously been reported. In this study, the genes for melatonin synthetic enzymes including tryptophan decarboxylase, tryptamine 5-hydroxylase (T5H), arylalkylamine N-acetyltransferase, and N-acetylserotonin methyltransferase were identified in Red Fuji apple. Each gene has several homologous genes. Sequence analysis shows that these genes have little homology with those of animals and they only have limited homology with known genes of rice melatonin synthetic enzymes. Multiple origins of melatonin synthetic genes during the evolution are expected. The expression of these genes is fully coordinated with melatonin production in apple development. Melatonin levels in apple exhibit an inverse relationship with the content of malondialdehyde, a product of lipid peroxidation. Two major melatonin synthetic peaks appeared on July 17 and on October 8 in both unbagged and bagged apple samples. At the periods mentioned above, apples experienced rapid expansion and increased respiration. These episodes significantly elevate reactive oxygen species production in the apple. Current data further confirmed that melatonin produced in apple was used to neutralize the toxic oxidants and protect the developing apple against oxidative stress.
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Enhanced cardioprotective effects mediated by plasmid containing the short-hairpin RNA of angiotensin converting enzyme with a biodegradable hydrogel after myocardial infarction.
J Biomed Mater Res A
PUBLISHED: 08-20-2013
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The expression of foreign gene was enhanced and prolonged by sustained releasing a target gene to cells from biodegradable dextran-poly(e-caprolactone)-2-hydroxylethylmethacrylate-poly(N-isopropylacrylamide) (Dex-PCL-HEMA/PNIPAAm) hydrogel in vitro. Moreover, we have demonstrated that injection of the same hydrogel improved post-infarct ventricular remodeling. Therefore, we hypothesized that intramyocardial injection of plasmid containing the short-hairpin RNA (shRNA) of angiotensin converting enzyme (ACE) with the same hydrogel enhances the cardioprotective effects superior to either alone or after rat myocardial infarction (MI). In this study, equal volume of phosphate-buffered solution (PBS), 10 ?g ACE-shRNA plasmids, hydrogel containing 10 ?g negative control ACE-shRNA plasmids and hydrogel containing 10 ?g ACE-shRNA plasmids were shortly injected into the infarct area of rats after MI, respectively. We found that ACE-shRNA plasmid-loaded hydrogel extended the duration of gene expression in vivo. Moreover, it was shown that direct intramyocardial injection of ACE-shRNA plasmid-loaded hydrogel significantly decreased the expression of local ACE expression, inhibited cell apoptosis, reduced infarct size, and improved cardiac function compared with the injection of either alone 30 days after MI in rats. These results suggest that injection of ACE-shRNA plasmid-loaded hydrogel into impaired myocardium obtains more cardioprotective effects than either alone in rat with MI by prolonging the gene silencing of ACE. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
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Enhancement of perovskite-based solar cells employing core-shell metal nanoparticles.
Nano Lett.
PUBLISHED: 08-19-2013
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Recently, inorganic and hybrid light absorbers such as quantum dots and organometal halide perovskites have been studied and applied in fabricating thin-film photovoltaic devices because of their low-cost and potential for high efficiency. Further boosting the performance of solution processed thin-film solar cells without detrimentally increasing the complexity of the device architecture is critically important for commercialization. Here, we demonstrate photocurrent and efficiency enhancement in meso-superstructured organometal halide perovskite solar cells incorporating core-shell Au@SiO2 nanoparticles (NPs) delivering a device efficiency of up to 11.4%. We attribute the origin of enhanced photocurrent to a previously unobserved and unexpected mechanism of reduced exciton binding energy with the incorporation of the metal nanoparticles, rather than enhanced light absorption. Our findings represent a new aspect and lever for the application of metal nanoparticles in photovoltaics and could lead to facile tuning of exciton binding energies in perovskite semiconductors.
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Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats.
J. Pineal Res.
PUBLISHED: 08-06-2013
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Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Identification of brown fat (beige/brite) in white adipose tissue (WAT) prompted us to investigate whether melatonin is a brown-fat inducer. We used Zücker diabetic fatty (ZDF) rats, a model of obesity-related type 2 diabetes and a strain in which melatonin reduces obesity and improves their metabolic profiles. At 5 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control and those treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk. Melatonin induced browning of inguinal WAT in both ZDF and ZL rats. Hematoxylin-eosin staining showed patches of brown-like adipocytes in inguinal WAT in ZDF rats and also increased the amounts in ZL animals. Inguinal skin temperature was similar in untreated lean and obese rats. Melatonin increased inguinal temperature by 1.36 ± 0.02°C in ZL and by 0.55 ± 0.04°C in ZDF rats and sensitized the thermogenic effect of acute cold exposure in both groups. Melatonin increased the amounts of thermogenic proteins, uncoupling protein 1 (UCP1) (by ~2-fold, P < 0.01) and PGC-1? (by 25%, P < 0.05) in extracts from beige inguinal areas in ZL rats. Melatonin also induced measurable amounts of UCP1 and stimulated by ~2-fold the levels of PGC-1? in ZDF animals. Locomotor activity and circulating irisin levels were not affected by melatonin. These results demonstrate that chronic oral melatonin drives WAT into a brown-fat-like function in ZDF rats. This may contribute to melatonins control of body weight and its metabolic benefits.
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One-pot construction of functional mesoporous silica nanoparticles for the tumor-acidity-activated synergistic chemotherapy of glioblastoma.
ACS Appl Mater Interfaces
PUBLISHED: 08-02-2013
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Mesoporous silica nanoparticles (MSNs) have proved to be an effective carrier for controlled drug release and can be functionalized easily for use as stimuli-responsive vehicles. Here, a novel intelligent drug-delivery system (DDS), camptothecin (CPT)-loaded and doxorubicin (DOX)-conjugated MSN (CPT@MSN-hyd-DOX), is reported via a facile one-pot preparation for use in synergistic chemotherapy of glioblastoma. DOX was conjugated to MSNs via acid-labile hydrazone bonds, and CPT was loaded in the pores of the MSNs. At pH 6.5 (analogous to the pH in tumor tissues), a fast DOX release was observed that was attributed to the hydrolysis of the hydrazone bonds. In addition, a further burst release of DOX was found at pH 5.0 (analogous to the pH in lyso/endosomes of tumor cells), leading to a strong synergistic effect. In all, CPT and DOX could be delivered simultaneously into tumor cells, and this intelligent DDS has great potential for tumor-trigged drug release for use in the synergistic chemotherapy of tumors.
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pH Responsive micelle self-assembled from a new amphiphilic peptide as anti-tumor drug carrier.
Colloids Surf B Biointerfaces
PUBLISHED: 07-22-2013
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An acid-responsive amphiphilic peptide that contains KKGRGDS sequence in hydrophilic head and VVVVVV sequence in hydrophobic tail was designed and prepared. In neutral or basic medium, this amphiphilic peptide can self-assemble into micelles through hydrogen bonding and hydrophobic interactions. If changing the solution pH to an acidic environment, the electrostatic repulsion interaction among the ionized lysine (K) residues will prevent the self-assembly of the amphiphilic peptide, leading to the dissociation of micelles. The anti-tumor drug of doxorubicin (DOX) was chosen and loaded into the self-assembled micelles of the amphiphilic peptide to investigate the influence of external pH change on the drug release behavior. As expected, the micelles show a sustained DOX release in neutral medium (pH 7.0) but fast release behavior in acidic medium (pH 5.0). When incubating these DOX-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD sequence to deliver the drug into HeLa cells. Combined with the low cytotoxicity of the amphiphilic peptide against both HeLa and COS7 cells, the amphiphilic peptide reported in this work may be promising in clinical application for targeted drug delivery.
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A Dual-Responsive Mesoporous Silica Nanoparticle for Tumor-Triggered Targeting Drug Delivery.
Small
PUBLISHED: 06-22-2013
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A novel pH- and redox- dual-responsive tumor-triggered targeting mesoporous silica nanoparticle (TTTMSN) is designed as a drug carrier. The peptide RGDFFFFC is anchored on the surface of mesoporous silica nanoparticles via disulfide bonds, which are redox-responsive, as a gatekeeper as well as a tumor-targeting ligand. PEGylated technology is employed to protect the anchored peptide ligands. The peptide and monomethoxypolyethylene glycol (MPEG) with benzoic-imine bond, which is pH-sensitive, are then connected via "click" chemistry to obtain TTTMSN. In vitro cell research demonstrates that the targeting property of TTTMSN is switched off in normal tissues with neutral pH condition, and switched on in tumor tissues with acidic pH condition after removing the MPEG segment by hydrolysis of benzoic-imine bond under acidic conditions. After deshielding of the MPEG segment, the drug-loaded nanoparticles are easily taken up by tumor cells due to the exposed peptide targeting ligand, and subsequently the redox signal glutathione in tumor cells induces rapid drug release intracellularly after the cleavage of disulfide bond. This novel intelligent TTTMSN drug delivery system has great potential for cancer therapy.
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A new anti-cancer strategy of damaging mitochondria by pro-apoptotic peptide functionalized gold nanoparticles.
Chem. Commun. (Camb.)
PUBLISHED: 06-12-2013
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Gold nanoparticles functionalized with pro-apoptotic peptide (PAP-AuNPs) were fabricated, which were able to lead to programmed cell-death by damaging mitochondria.
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A walnut-enriched diet reduces the growth of LNCaP human prostate cancer xenografts in nude mice.
Cancer Invest.
PUBLISHED: 06-11-2013
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It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet.
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Photo-switched self-assembly of a gemini ?-helical peptide into supramolecular architectures.
Nanoscale
PUBLISHED: 06-05-2013
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An azobenzene-linked symmetrical gemini ?-helical peptide was designed and prepared to realize the light-switched self-assembly. With the reversible molecular structure transition between Z- and U-structures, the morphology of the self-assembled gemini ?-helical peptide can reversibly change between nanofibers and nanospheres in acidic medium, and between nanospheres and vesicles in basic medium.
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Effects of melatonin on superovulation and transgenic embryo transplantation in small-tailed han sheep (Ovis aries).
Neuro Endocrinol. Lett.
PUBLISHED: 06-01-2013
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In this study, the effects of melatonin on superovulation and the transfer of transgenic embryos were investigated in Small-Tailed Han sheep.
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Theranostic GO-Based Nanohybrid for Tumor Induced Imaging and Potential Combinational Tumor Therapy.
Small
PUBLISHED: 05-24-2013
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Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function.
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Controlled arrays of self-assembled peptide nanostructures in solution and at interface.
Langmuir
PUBLISHED: 05-24-2013
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Controlling the formation of large and homogeneous arrays of bionanostructures through the self-assembly approach is still a great challenge. Here, we report the spontaneous formation of highly ordered arrays based on aligned peptide nanostructures in a solution as well as at an interface by self-assembly. By controlling the time and temperature of self-assembly in the solution, parallel fibrous alignments and more sophisticated two-dimensional "knitted" fibrous arrays could be formed from aligned rod-like fibers. During the formation of such arrays, the "disorder-to-order" transitions are controlled by the temperature-responsible motile short hydrophobic tails of the gemini-like amphiphilic peptides (GAPs) with asymmetric molecular conformation. In addition, the resulting long-range-ordered "knitted" fibrous arrays are able to direct mineralization of calcium phosphate to form organic-inorganic composite materials. In this study, the self-assembly behavior of these peptide building blocks at an interface was also studied. Highly ordered spatial arrays with vertically or horizontally aligned nanostructures such as nanofibers, microfibers, and microtubes could be formed through interfacial assembly. The regular structures and their alignments on the interface are controlled by the alkyl chain length of building blocks and the hydrophilicity/hydrophobicity property of the interface.
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Peptide-based vector of VEGF plasmid for efficient gene delivery in vitro and vessel formation in vivo.
Bioconjug. Chem.
PUBLISHED: 05-21-2013
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Critical limb ischemia is regarded as a potentially lethal disease, and the treatment effects of existing therapies are limited. Here, in order to develop a potential approach to improve the therapy effects, we designed a peptide of TAT-PKKKRKV as the vector for VEGF165 plasmid to facilitate in vivo angiogenesis. In in vitro studies, TAT-PKKKRKV with low cytotoxicity exhibited efficient transfection ability either with or without serum. Additionally, application of TAT-PKKKRKV/VEGF165 complexes in hindlimb ischemia rats obviously promoted the expression of VEGF protein, which further enhanced effective angiogenesis. The results indicated that TAT-PKKKRKV is an efficient gene vector with low toxicity both in vitro and in vivo, which has great potential for clinical gene therapy.
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Therapeutic nanomedicine based on dual-intelligent functionalized gold nanoparticles for cancer imaging and therapy in vivo.
Biomaterials
PUBLISHED: 05-08-2013
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A novel strategy to construct a therapeutic system based on functionalized AuNPs which can specifically respond to tumor microenvironment was reported. In the therapeutic system, doxorubicin was conjugated to AuNPs via thiol-Au bond by using a peptide substrate, CPLGLAGG, which can be specifically cleaved by the protease. In vivo study shows that after injection of the functionalized AuNPs to the tumor-bearing mice, the over-expressed protease of MMP-2 in tumor tissue and intracellular GSH can lead to the rapid release of the anti-tumor drug (doxorubicin) from the functionalized AuNPs to inhibit tumor growth and realize fluorescently imaging simultaneously. The functionalized AuNPs with tumor-triggered drug release property can further improve the efficacy and reduce side effects significantly.
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In situ recognition of cell-surface glycans and targeted imaging of cancer cells.
Sci Rep
PUBLISHED: 05-01-2013
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Fluorescent sensors capable of recognizing cancer-associated glycans, such as sialyl Lewis X (sLe(x)) tetrasaccharide, have great potential for cancer diagnosis and therapy. Studies on water-soluble and biocompatible sensors for in situ recognition of cancer-associated glycans in live cells and targeted imaging of cancer cells are very limited at present. Here we report boronic acid-functionalized peptide-based fluorescent sensors (BPFSs) for in situ recognition and differentiation of cancer-associated glycans, as well as targeted imaging of cancer cells. By screening BPFSs with different structures, it was demonstrated that BPFS? with a FRGDF peptide could recognize cell-surface glycan of sLe(x) with high specificity and thereafter fluorescently label and discriminate cancer cells through the cooperation with the specific recognition between RGD and integrins. The newly developed peptide-based sensor will find great potential as a fluorescent probe for cancer diagnosis.
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[Sequence analysis of cisAB06, an ABO blood subtype].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 04-10-2013
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To investigate serological and genetic characteristics for an individual with cisAB06, an ABO blood subtype.
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Bioreducible polypeptide containing cell-penetrating sequence for efficient gene delivery.
Pharm. Res.
PUBLISHED: 03-27-2013
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To design excellent polypeptide-based gene vectors and determine the gene delivery efficiency.
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Multifunctional Envelope-Type Mesoporous Silica Nanoparticles for Tumor-Triggered Targeting Drug Delivery.
J. Am. Chem. Soc.
PUBLISHED: 03-19-2013
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A novel type of cellular-uptake-shielding multifunctional envelope-type mesoporous silica nanoparticle (MEMSN) was designed for tumor-triggered targeting drug delivery to cancerous cells. ?-Cyclodextrin (?-CD) was anchored on the surface of mesoporous silica nanoparticles via disulfide linking for glutathione-induced intracellular drug release. Then a peptide sequence containing Arg-Gly-Asp (RGD) motif and matrix metalloproteinase (MMP) substrate peptide Pro-Leu-Gly-Val-Arg (PLGVR) was introduced onto the surface of the nanoparticles via host-guest interaction. To protect the targeting ligand and prevent the nanoparticles from being uptaken by normal cells, the nanoparticles were further decorated with poly(aspartic acid) (PASP) to obtain MEMSN. In vitro study demonstrated that MEMSN was shielded against normal cells. After reaching the tumor cells, the targeting property could be switched on by removing the PASP protection layer via hydrolyzation of PLGVR at the MMP-rich tumor cells, which enabled the easy uptake of drug-loaded nanoparticles by tumor cells and subsequent glutathione-induced drug release intracellularly.
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Peripheral reproductive organ health and melatonin: ready for prime time.
Int J Mol Sci
PUBLISHED: 02-25-2013
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Melatonin has a wide variety of beneficial actions at the level of the gonads and their adnexa. Some actions are mediated via its classic membrane melatonin receptors while others seem to be receptor-independent. This review summarizes many of the published reports which confirm that melatonin, which is produced in the ovary, aids in advancing follicular maturation and preserving the integrity of the ovum prior to and at the time of ovulation. Likewise, when ova are collected for in vitro fertilization-embryo transfer, treating them with melatonin improves implantation and pregnancy rates. Melatonin synthesis as well as its receptors have also been identified in the placenta. In this organ, melatonin seems to be of particular importance for the maintenance of the optimal turnover of cells in the villous trophoblast via its ability to regulate apoptosis. For male gametes, melatonin has also proven useful in protecting them from oxidative damage and preserving their viability. Incubation of ejaculated animal sperm improves their motility and prolongs their viability. For human sperm as well, melatonin is also a valuable agent for protecting them from free radical damage. In general, the direct actions of melatonin on the gonads and adnexa of mammals indicate it is an important agent for maintaining optimal reproductive physiology.
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Effects of acupuncture on heart rate variability in beagles; preliminary results.
Evid Based Complement Alternat Med
PUBLISHED: 02-24-2013
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Evidence-based animal experimental research concerning the effects of acupuncture on autonomic function was performed by two research teams from China and Austria. This study describes measurements in beagles. Heart rate variability (HRV) recordings were performed under stable conditions in Beijing, China, and the data analysis and interpretation were completed in Graz, Austria. The electrocardiograms were recorded during bilateral body acupuncture (PC6, Neiguan). Power of the low frequency (LF), high frequency (HF), and the ratio (LF/HF) changed significantly during acupuncture stimulation in beagles after injection of atropine and ? -blocker. However, there was no significant change in HF power after needling the Neiguan acupoint when a cervical vagotomy has been performed. Our findings show that acupuncture can mediate the HRV even after pharmaceutical blocking of autonomic function. Acupuncture effects on HRV should rely not only on autonomic nervous system but on complete central nervous system.
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Oligoamines grafted hyperbranched polyether as high efficient and serum-tolerant gene vectors.
Colloids Surf B Biointerfaces
PUBLISHED: 02-22-2013
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To develop low toxic, high efficient, and excellent serum-tolerant polycation gene delivery systems, a series of oligoamines grafted hyperbranched polyether (oligoamines-g-HBP) were synthesized by conjugating different oligoamines, including triethylenetetramine (TETA) and tetraethylenepentamine (TEPA), onto COOH-functionalized hyperbranched poly(3-ethyl-3-oxetanemethanol). It was found that oligoamines-g-HBP exhibited good buffering capacity, strong DNA binding and high resistance against protein adsorption. In vitro cytotoxicity measurement indicated that oligoamines-g-HBP had much lower cytotoxicity as compared with 25kDa PEI. The transfection efficiency of TEPA-g-HBP/DNA complexes at a certain N/P ratio was significantly higher than that of 25kDa PEI/DNA complexes. Interestingly, it was found that TEPA-g-HBP had much improved serum-tolerant capability as compared with 25kDa PEI even when serum concentration was increased to 30%. Confocal laser images further showed that the amount of YOYO-1 labeled DNA in nuclei got increased with increasing the number of secondary amino ethylene groups in oligoamines-g-HBP. The oligoamines-g-HBP presented great potential as gene delivery vectors for further clinical applications.
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Electroacupuncture at Zusanli (ST36) Prevents Intestinal Barrier and Remote Organ Dysfunction following Gut Ischemia through Activating the Cholinergic Anti-Inflammatory-Dependent Mechanism.
Evid Based Complement Alternat Med
PUBLISHED: 01-11-2013
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This study investigated the protective effect and mechanism of electroacupuncture at ST36 points on the intestinal barrier dysfunction and remote organ injury after intestinal ischemia and reperfusion injury in rats. Rats were subjected to gut ischemia for 30?min, and then received electroacupuncture for 30?min with or without abdominal vagotomy or intraperitoneal administration of cholinergic ? 7 nicotinic acetylcholine receptor ( ? 7nAChR) inhibitor. Then we compared its effects with electroacupuncture at nonchannel points, vagal nerve stimulation, or intraperitoneal administration of cholinergic agonist. Cytokine levels in plasma and tissue of intestine, lung, and liver were assessed 60?min after reperfusion. Intestinal barrier injury was detected by histology, gut injury score, the permeability to 4?kDa FITC-dextran, and changes in tight junction protein ZO-1 using immunofluorescence and Western blot. Electroacupuncture significantly lowered the levels of tumor necrosis factor- ? and interleukin-8 in plasma and organ tissues, decreased intestinal permeability to FITC-dextran, and prevented changes in ZO-1 protein expression and localization. However, abdominal vagotomy or intraperitoneal administration of cholinergic ? 7nAChR inhibitor reversed these effects of electroacupuncture. These findings suggest that electroacupuncture attenuates the systemic inflammatory response through protection of intestinal barrier integrity after intestinal ischemia injury in the presence of an intact vagus nerve.
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Graphene-based anticancer nanosystem and its biosafety evaluation using a zebrafish model.
Biomacromolecules
PUBLISHED: 01-11-2013
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In this paper, a facile strategy to develop graphene-based delivery nanosystems for effective drug loading and sustained drug release was proposed and validated. Specifically, biocompatible naphthalene-terminated PEG (NP) and anticancer drugs (curcumin or doxorubicin (DOX)) were simultaneously integrated onto oxidized graphene (GO), leading to self-assembled, nanosized complexes. It was found that the oxidation degree of GO had a significant impact on the drug-loading efficiency and the structural stability of nanosystems. Interestingly, the nanoassemblies resulted in more effective cellular entry of DOX in comparison with free DOX or DOX-loaded PEG-polyester micelles at equivalent DOX dose, as demonstrated by confocal microscopy studies. Moreover, the nanoassemblies not only exhibited a sustained drug release pattern without an initial burst release, but also significantly improved the stability of formulations which were resistant to drug leaking even in the presence of strong surfactants such as aromatic sodium benzenesulfonate (SBen) and aliphatic sodium dodecylsulfonate (SDS). In addition, the nanoassemblies without DOX loading showed negligible in vitro cytotoxicity, whereas DOX-loaded counterparts led to considerable toxicity against HeLa cells. The DOX-mediated cytotoxicity of the graphene-based formulation was around 20 folds lower than that of free DOX, most likely due to the slow DOX release from complexes. A zebrafish model was established to assess the in vivo safety profile of curcumin-loaded nanosystems. The results showed they were able to excrete from the zebrafish body rapidly and had nearly no influence on the zebrafish upgrowth. Those encouraging results may prompt the advance of graphene-based nanotherapeutics for biomedical applications.
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Synergistic gene and drug tumor therapy using a chimeric peptide.
Biomaterials
PUBLISHED: 01-06-2013
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Co-delivery of gene and drug for synergistic therapy has provided a promising strategy to cure devastating diseases. Here, an amphiphilic chimeric peptide (Fmoc)2KH7-TAT with pH-responsibility for gene and drug delivery was designed and fabricated. As a drug carrier, the micelles self-assembled from the peptide exhibited a much faster doxorubicin (DOX) release rate at pH 5.0 than that at pH 7.4. As a non-viral gene vector, (Fmoc)(2)KH(7)-TAT peptide could satisfactorily mediate transfection of pGL-3 reporter plasmid with or without the existence of serum in both 293T and HeLa cell-lines. Besides, the endosome escape capability of peptide/DNA complexes was investigated by confocal laser scanning microscopy (CLSM). To evaluate the co-delivery efficiency and the synergistic anti-tumor effect of gene and drug, p53 plasmid and DOX were simultaneously loaded in the peptide micelles to form micelleplexes during the self-assembly of the peptide. Cellular uptake and intracellular delivery of gene and drug were studied by CLSM and flow cytometry respectively. And p53 protein expression was determined via Western blot analysis. The in vitro cytotoxicity and in vivo tumor inhibition effect were also studied. Results suggest that the co-delivery of gene and drug from peptide micelles resulted in effective cell growth inhibition in vitro and significant tumor growth restraining in vivo. The chimeric peptide-based gene and drug co-delivery system will find great potential for tumor therapy.
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The influence of zusanli and nonmeridian acupuncture points on the survival rate and intestinal tissue features after fatal hemorrhagic shock in rats.
Evid Based Complement Alternat Med
PUBLISHED: 01-04-2013
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Sixty Sprague-Dawley rats were divided into 5 groups: (a) control group (HS); (b) Immediate rehydration group (IFR); (c) ST36 electroacupuncture (EA) delay rehydration group (EA/DFR): EA at ST36 immediately after blood loss with infusion 3?h later; (d) EA nonmeridian rehydration group (SEA/DFR): EA at nonacupuncture sites with rehydration similar to EA/DFR; (e) ST36 EA group (EA): EA at ST36 immediately after blood loss with no rehydration. Forty-five percent of the entire blood volume was taken out to make lethal hemorrhagic shock models. We recorded the survival rate, intestinal tissue DAO content, and microcirculation. The survival rate of the EA/DFR group and the IFR group was significantly higher than that of the other three groups (P < 0.05). Twelve hours after blood loss, intestinal tissue DAO content of the EA/DFR group and the IFR group was significantly higher than that of the SEA/DFR group, EA group, and HS group (P < 0.05 and P < 0.01). The mucosal blood flow of the EA/DFR group and the IFR group was significantly higher than the other groups (P < 0.05 each). We conclude that EA improves the blood pressure and raises the early survival rate of hemorrhagic shock rats, maintains the intestinal barrier function, and improves the degree of intestinal ischemia.
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Enhanced nuclear import and transfection efficiency of TAT peptide-based gene delivery systems modified by additional nuclear localization signals.
Bioconjug. Chem.
PUBLISHED: 12-21-2011
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Cellular uptake and nuclear localization are two major barriers in gene delivery. In order to evaluate whether additional nuclear localization signals (NLSs) can improve gene transfection efficiency, we introduced different kinds of NLSs to TAT-based gene delivery systems to form three kinds of complexes, including TAT-PV/DNA, TAT/DNA/PV, and TAT/DNA/HMGB1. The DNA binding ability of different vectors was evaluated by agarose gel electrophoresis. The in vitro transfections mediated by different complexes under different conditions were carried out. The cells treated by different complexes were observed by confocal microscopy. The MTT assay showed that all complexes did not exhibit apparent cytotoxicity in both HeLa and Cos7 cell lines even at high N/P ratios. The luciferase reporter gene expression mediated by TAT-PV/DNA complexes exhibited about 200-fold enhancement as compared with TAT/DNA complexes. Confocal study showed that, except TAT/DNA/PV, all other complexes exhibited enhanced nuclear accumulation and cellular uptake in both HeLa and Cos7 cell lines. These results indicated that the introduction of nuclear localization signals could enhance the transfection efficacy of TAT-based peptides, implying that the TAT peptide-based vectors demonstrated here have promising potential in gene delivery.
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