Search

Lipid accumulation, oxidative stress, and inflammation in hepatocytes are features of nonalcoholic fatty liver disease (NAFLD). Garcinia biflavonoid 1a (GB1a) is a natural product capable of hepatic protection. In this study, the effect of GB1a on anti-inflammatory, antioxidant, and regulation of the accumulation in HepG2 cells and mouse primary hepatocytes (MPHs) was investigated, and its regulatory mechanism was further explored. The result showed that GB1a reduced triglyceride (TG) content and lipid accumulation by regulating the expression of SREBP-1c and PPARα; GB1a reduced reactive oxygen species (ROS) and improved cellular oxidative stress to protect mitochondrial morphology by regulating genes Nrf2, HO-1, NQO1, and Keap1; and GB1a reduced the damage of hepatocytes by inhibiting the expression of inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65. The activities of GB1a were lost in liver SIRT6-specific knockout mouse primary hepatocytes (SIRT6-LKO MPHs). This indicated that activating SIRT6 was critical for GB1a to perform its activity, and GB1a acted as an agonist of SIRT6. It was speculated that GB1a may be a potential drug for NAFLD treatment.

cerebral malaria (CM) is an important complication of malaria with a high mortality rate. Artesunate is recommended as the first-line artemisinin compound treatment for severe malaria. Due to the difficulty of obtaining brain tissue samples clinically, the use of animals to research host responses to CM parasite infections is necessary. Rodent malaria models allow for detailed time series studies of host responses in multiple organs. To date, studies on the transcriptome of severe malaria are only limited to the parasites in the peripheral blood of patients, and there is little data on the transcriptional changes in brain tissue in mice with CM treated with artesunate.in this study, fresh tissue samples (three biological replicates per mouse) from the same area of the brain in each animal were collected from the uninfected,the mechanism of improving the prognosis of cerebral malaria by artesunate may not only involve the killing of plasmodium but also the inhibition of a cytokine storm in the host. This study provides new insights into the molecular mechanism by which artesunate improves the prognosis of cerebral malaria.

Shaoqin Zheng1,2 *, Yuan Liang2 *, Zhaojia Wang,1 Min Liu,1 Yingyi Chen,1 Ying Ai,1 Wenfeng Guo,1,3 Guoming Li,1 Yueming Yuan,1,2 Zhiyong Xu,2 Wanting Wu,1 Xinan Huang,1,3 Zhibing Wu,3 Qin Xu,1,3 Jianping Song,1,3 Changsheng Deng1,3 1Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Science and Technology Institute, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianping Song; Changsheng Deng, Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China, Tel +86-20-3658 5633 ; +86-20-8746 1723, Email songjp@gzucm.edu.cn; dcs19811202@163.comIntroduction: Artemisinin-based combination therapies (ACTs) act as first-line antimalarial drugs and play a crucial role in the successful control of falciparum malaria. However, the recent emergence of resistance of Plasmodium falciparum to ACTs in South East Asia is of particular concern. Hence, there is an urgent need to identify the genetic determinants of and understand the molecular mechanisms underpinning such resistance. Artemisinin resistance (AR) is primarily driven by the mutations in the P. falciparum K13 protein, which is widely recognized as the major molecular marker of AR. However, association of K13 mutations with in vivo AR has been ambiguous due to the absence of a tractable model.Methods: In this study, we have successfully produced artemisinin- and piperaquine-resistant P. berghei K173 following drug administrations. Prolonged parasite clearance and early recrudescence were found following daily exposure to high doses of artemisinin and piperaquine. We have also sequenced the DNA of artemisinin-resistant strains and piperaquine-resistant strains of P. berghei K173 to explore the relationship between PfK13 and AR.Results: The resistance index of P. berghei K173 reached 12.4 after 30 artemisinin-resistant generations, but AR declined gradually after 30 generations. On the 50th generation, the resistance index of artemisinin-resistant strains was only 5.0 compared with the severe drug resistance of piperaquine-resistant strains (I90=148.8). DNA sequencing of artemisinin-resistant strains showed that there were 9 meaningful mutations at P. berghei K13-propeller domain, but the above mutations did not include common clinical point mutations.Conclusion: Our data show that artemisinin is less susceptible to severe resistance compared with other antimalarial drugs. In addition, mutation on P. berghei K13 has a multi-drug-resistant phenotype and may be used as a biomarker to monitor its resistance. More studies need to be conducted on the new mutations detected so as to understand their association, if any, with ACT resistance.Keywords: malaria, Plasmodium berghei, P. berghei K13 gene, artemisinin resistance

Herbal tea is a highly popular and widely consumed beverage. However, a pain-relieving and fever-reducing drug, acetophenetidin, was recently found to illegally occur in herbal tea for a fraud purpose. Due to the potential health risk and urgent requirement for on-site screening method, a one-step and high specificity strip for identifying acetophenetidin was developed for the first time. Assisted by computational chemistry, four haptens were designed to prepare immunogens and coating antigens for antibody generation, and a specific antibody with ultra-sensitivity and high specificity was generated, showing half maximal inhibitory (IC50) of 16.46 ng/mL for acetophenetidin, less than 3.5% of cross-reactivity to analogs by ELISA. A gold nanoparticles immunochromatographic strip was developed for detection of acetophenetidin in herbal tea, demonstrating a cut-off value of 160 ng/mL and a limit of detection of 1.63 ng/mL. The recovery rates were ranged from 102.2% to 106.1% with coefficient of variation between 2.21% and 7.20%. The analysis of real samples (n = 20) by the strip was well correlated with that of the confirmatory method, liquid chromatography−tandem mass spectrometry. The proposed strip has the potential to be used for rapid screening of acetophenetidin in herbal tea.

Cell-derived vesicles retain the cytoplasm and much of the native cell membrane composition. Therefore, they are attractive for investigations of membrane biophysics, drug delivery systems, and complex molecular factories. However, their fragility and aggregation limit their applications. Here, the mechanical properties and stability of giant plasma membrane vesicles (GPMVs) are enhanced by decorating them with a specifically designed diblock copolymer, cholesteryl-poly[2-aminoethyl methacrylate-b-poly(ethylene glycol) methyl ether acrylate]. When cross-linked, this polymer brush enhances the stability of the GPMVs. Furthermore, the pH-responsiveness of the copolymer layer allows for a controlled cargo loading/release, which may enable various bioapplications. Importantly, the cross-linked-copolymer GPMVs are not cytotoxic and preserve in vitro membrane integrity and functionality. This effective strategy to equip the cell-derived vesicles with stimuli-responsive cross-linkable copolymers is expected to open a new route to the stabilization of natural membrane systems and overcome barriers to biomedical applications., Advanced Healthcare Materials, 11 (23), ISSN:2192-2640, ISSN:2192-2659

Proteases, as one of the most significant kind of digestive enzymes, are closely related to a variety of physiological processes and diseases. Herein, a black phosphorus nanosheets (BPs) based sensitive fluorometric method for protease detection and inhibitor screening is proposed. The aqueous solution of perylene probe (probe 1) displays a strong fluorescence. BPs, as novel discovered two-dimensional (2D) materials, can adsorb probe 1 through electrostatic interactions, which causes fluorescence quenching of probe 1. Histone can control the interactions between the perylene probe and BPs, which can be further regulated by the introduction of a protease. Thus, the protease activity can be monitored by detecting the fluorescence intensity changes of probe 1. The method is label free, sensitive and selective. As low as 1 ng/mL trypsin can be easily detected.

A ratiometric nanosensor for the selective detection and intracellular imaging of highly reactive oxygen species (hROS) is developed. Benzoperylene probe and Mn-ZnS quantum dots based nanoparticles were fabricated through cost effective and simple procedures. The nanoparticles exhibit distinct excimer emission and long-lived room-temperature phosphorescence (RTP) emission at the same time under single wavelength excitation. The nanosensor shows highly sensitive and selective ratiometric response towards hROS over other ROS. The dual emission property also endows the nanoparticles the capability for sensitive live cell imaging of hROS, and the potential for real time monitoring of intracellular hROS.

A sensitive sandwich immunoassay for the sensing of human epididymis protein 4 (HE4) is developed based on aggregation-induced emission probe doped silica nanoparticles. Fluorescent silica nanoparticles (TSiO2) with excellent performance were prepared using a tetraphenylethylene based probe (TPE-C4-4) to produce a controlled aggregation effect, and HE4 was detected using antibody-functionalized fluorescent silica nanoparticles. The fluorescent silica nanoparticles possess good photophysical properties. The TSiO2 NPs were surface modified with carboxyl groups, and the antibody was covalently attached onto the surface of the nanoparticles. In addition, magnetic beads were modified with N-hydroxysulfosuccinimide sodium salt (NHS) on their surface, capable of forming stable peptide bonds with the antibody. TSiO2 NPs modified by an antibody and the magnetic beads modified by an antibody were used for the sandwich immunoassay for HE4 protein. The assay is quite sensitive and selective. The detection limit of HE4 is estimated to be 40 pM. The assay shows promising applications for the early diagnosis of ovarian cancer and the development of ovarian cancer-related drugs.

Additional file 1.

Background Malaria is a major public health problem in Togo. Guangzhou University of Chinese medicine of China, and the Ministry of Health and Social Security of Togo launched a nationwide artemisinin compound Mass Drug Administration Project in East Mono with a population of 150,000. Before launching the project, the sensitivity test of artemisinin piperaquine tablet was conducted in Elawagnon general clinic. On this background, we evaluated the efficacy and safety of artemisinin piperaquine in the treatment of uncomplicated falciparum malaria in children under five years of age. Methods In this study, children aged 6-59 months without complications of falciparum malaria were observed, and the selected cases were treated with artemisinin piperaquine. The patients were followed up for 28 days to observe the fever clearance time, parasitemia, gametophyte, cure rate, haemoglobin and msp-2 gene polymorphism. The primary end point was the 28-day cure rate, and PCR corrected reinfection and recrudescence. This research was conducted according to standardized WHO protocol for the assessment of the efficacy of anti-malarial treatment. Results A total of 91 children participated in the study. The adequate clinical and parasitological response (ACPR) before PCR-corrected were 66 (72.52%) and 90 (98.90%) after PCR-corrected. The patient was well tolerated to artemisinin piperaquine and no serious adverse reactions were observed. The average hemoglobin level increased by 0.05g/dl per day (p< 0.0001). The gametophyte doesn’t declined at the beginning of treatment, however, 14 days later, it dropped(D21:p

Background and purpose Activation of the human pregnane X receptor (PXR; NR1I2) has potential therapeutic uses for inflammatory bowel disease (IBD). Imperatorin (IMP), a naturally occurring coumarin, is the main bioactive ingredient of Angelica dahurica Radix, which is regularly used to treat the common cold and intestinal disorders. However, there are no data on the protective effects of IMP against IBD. Experimental approach The effects of IMP on PXR-modulated cytochrome P450 3A4 (CYP3A4) expression were assessed using a PXR transactivation assay, a mammalian two-hybrid assay, a competitive ligand-binding assay, analysis of CYP3A4 mRNA and protein expression levels and measurement of CYP3A4 activity using a cell-based reporter gene assay and in vitro model. The inhibitory effects of IMP on NF-κB activity were evaluated by a reporter assay and NF-κB p65 nuclear translocation. The anti-IBD effects of IMP were investigated in a dextran sulphate sodium (DSS)-induced colitis mouse model. Colon inflammatory cytokines were assessed by elisa. Key results IMP activated CYP3A4 promoter activity, recruited steroid receptor coactivator 1 to the ligand-binding domain of PXR and increased the expression and activity of CYP3A4. PXR knockdown substantially reduced IMP-induced increase in CYP3A4 expression. Furthermore, IMP-mediated PXR activation suppressed the nuclear translocation of NF-κB and down-regulated LPS-induced expression of pro-inflammatory genes. Nevertheless, PXR knockdown partially reduced the IMP-mediated inhibition of NF-κB. IMP ameliorated DSS-induced colitis by PXR/NF-κB signalling. Conclusions and implications IMP acts as a PXR agonist to attenuate DSS-induced colitis by suppression of the NF-κB-mediated pro-inflammatory response in a PXR/NF-κB-dependent manner.

A novel and efficient approach has been established for the synthesis of silver nanoclusters capped silica nanoparticles (SiO 2 @AgNCs). These nanoclusters (AgNCs) capped silica nanoparticles were utilized as a novel ratiometric photoluminescence (PL) nanosensor for extremely sensitive and selective detection of I − and S 2− ions. The AgNCs were prepared in situ on the silica nanoparticles through polyethyleneimine (PEI) template approach. While dual PL emissions of AgNCs (at 500 nm) and luminescent silica nanoparticles (at 602 nm) formed the basis for the ratiometric sensing. The PL emission of AgNCs was strongly quenched by I − (or S 2− ), while that of luminescent silica nanoparticles was hardly affected. The PL emission intensity ratio of AgNCs and the luminescent silica nanoparticles was defined as I 500 /I 602 . A good linear relationship between the I 500 /I 602 value and the concentration of I − (or S 2− ) was observed, and the limit of detection (LOD) was estimated to be 57 nM for I − and 62 nM for S 2− . In addition, the fluorescence images of the SiO 2 @AgNCs nanosensor changed from white to orange upon exposure to different concentrations of I − (or S 2− ) (0–250 μM), which could be clearly distinguished by the naked eye. The SiO 2 @AgNCs nanosensor exhibited good selectivity against other analytes, and I − or S 2− ions could be separately detected via the introduction of proper masking agents. Furthermore, the detection of I − and S 2− in real water samples was also demonstrated.

A fluorescence turn-on assay for alkaline phosphatase (ALP) activity is developed through the controlled release of polyethyleneimine-capped copper nanoclusters (PEI-capped CuNCs) from the MnO2 nanosheets. In an aqueous solution, the positively charged PEI-capped CuNCs could be adsorbed onto the surface of the negatively charged MnO2 nanosheets. Such adsorption through favorable electrostatic interactions could efficiently quench the nanocluster fluorescence emission via resonance energy transfer from the PEI-capped CuNCs to the MnO2 nanosheets. 2-Phospho-l-ascorbic acid (AAP) could be hydrolyzed to l-ascorbic acid (AA) in the presence of ALP. AA could reduce MnO2 into Mn2+ and trigger the disintegration of the MnO2 nanosheets. As a result, the CuNCs were released and the quenched fluorescence was recovered efficiently. The detection strategy is simple, inexpensive, sensitive, selective, with low toxicity, and has better biocompatibility. The newly fabricated biosensor for ALP activity will potentially make it a robust candidate for numerous biological and biomedical applications.

A sensitive and selective luminescent nanoprobe (referred to as DEPN) is designed for the determination of Cu(II) ions. DEPN shows two emission peaks, one at 602 nm and caused by [Ru(bpy)3]2+, the other (peaking at 500 nm) caused by silver nanoclusters (AgNCs). The luminescence of the ruthenium complex is inert and acts as the internal reference signal, while that of the AgNCs is quenched by Cu(II) ions. Under 350 nm photoexcitation, a linear relationship is found between the ratio of emission intensity (I500/I602) and the concentration of Cu(II) ions in the 0.1–16 μM range. The detection limit of Cu(II) ions is estimated to be 50 nM. The DEPN was applied to the determination of Cu(II) ions in (spiked) water samples, and to intracellular imaging of Cu(II) in HeLa cells using confocal fluorescence microscopy.

A bright white light emitting benzoperylene probe-polyethyleneimine capped quantum dot nanocomposite has been synthesized for the first time. The negatively charged benzoperylene probe with a carboxylic acid functional group tends to self-assemble in the presence of a polycation, and exhibits distinct induced excimer fluorescence. Phosphorescence emitting manganese doped zinc sulfide quantum dots (Mn-ZnS QDs) were capped with polyethyleneimine (PEI). The PEI capped Mn-ZnS QDs were used to induce the benzoperylene probe self-assembly. A bright white light emitting nanocomposite was obtained both in solution and in solid state. The white emission has Commission Internationale de l'Eclairage (CIE) coordinates of (0.33, 0.32), a color-rendering index (CRI) of 72.61 and correlated color temperature (CCT) of 5697 K. Multiple color emissions from blue to orange could also be obtained in a controllable manner via simple adjustment of the ratio of the PEI capped Mn-ZnS QDs and the benzoperylene probe. The nanocomposite displays good photo, chemical and long-term stability. A strong white light emitting LED device based on the nanocomposite was demonstrated.

AIDS, a serious fatal disease caused by the human immunodeficiency virus (HIV), is an epidemic disease for which no effective vaccine has been established. The current therapeutic interventions for AIDS have limited efficacy because they are unable to clear HIV infections and the continuous occurrence of resistant HIV strains. Therefore, the exploitation of new drugs to prevent the spread of AIDS remains a high priority. In this study, the effects of icariin and its metabolite anhydroicaritin on SIV/HIV replication were investigated. In CEM × 174 cells and PBMC cells, both icariin and anhydroicaritin can significantly inhibit HIV-1 or SIVmac251 replication. Furthermore, molecular docking studies revealed that icariin and anhydroicaritin can act on both HIV reverse transcriptase and protease but could not bind to integrase. Reverse transcriptase and protease inhibition biological assays showed that both icariin and anhydroicaritin could significantly inhibit only HIV reverse transcriptase. In summary, the two compounds can significantly inhibit HIV/SIV in vitro and their targets may be mainly involved with HIV reverse transcriptase.

Three pairs of new spirocyclic alkaloid enantiomers eurotinoids A–C (1–3), as well as a known biogenetically related racemate dihydrocryptoechinulin D (4) were isolated from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures were determined by spectroscopic analyses and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first two “meta” products from a non-stereoselective [4 + 2] Diels-Alder cycloaddition presumably between an enone group of a diketopiperazine alkaloid and a diene group of a benzaldehyde derivative via a new head-to-tail coupling mode biosynthetically, while 3 and 4 were “ortho” products. Their enantiomers exhibited different antioxidative and cytotoxic activities. The modes of action were investigated by a preliminary molecular docking study.

In this work, we report a novel sensor for colorimetric and fluorometric H2O2 sensing which is based on silver nanoparticles decorated and tetraphenylethene probe doped silica nanoparticles (Ag@TPE-SiO2 NPs). A positively charged tetraphenylethene (TPE) probe is doped into silica nanoparticles, and the nanoparticles exhibit strong fluorescence emission due to aggregation-induced emission (AIE) of the TPE probe. Ag nanoparticles (AgNPs) are prepared in situ on the surface of the silica nanoparticles. AgNPs serve as a nanoquencher which can quench the AIE emission of the TPE-SiO2 NPs efficiently. However, AgNPs can be oxidized to Ag+ by H2O2, which leads to fluorescence recovery and color fading of the Ag@TPE-SiO2 NPs. The dual-readout strategy allows sensitive analysis of H2O2. The detection limit of the fluorometric and colorimetric assay is 0.28 and 2.1 μM, respectively. And the nanosensor also shows good selectivity. In addition, analysis of H2O2 in human serum and intracellular imaging of H2O2 are both demonstrated. With the good analytical properties of merit, the proposed nanoprobe has a promising potential for H2O2 related bioanalysis and biomedical applications.

A novel and efficient approach has been established for the synthesis of silver nanoclusters capped silica nanoparticles (SiO

In this work, the α-conformation (individual locally separated chain) of the conjugated polymer poly(9,9-dioctylfluorene) (PFO) in dilute solution is studied by the following three points: the Mark-Houwink exponent a, the fractal dimension D, and the form factor R(g)/R(h). From the result of a, the α-conformation of PFO is considered to have a semirigid chain conformation in dilute solution. We establish the mathematical relationship between the Mark-Houwink exponent a and the fractal dimension D in dilute solution. To prove the rationality of this mathematical relationship, the classic polymer polystyrene (PS) is used for comparison. According to the result of D, it can be known that the α-conformation of PFO has a relatively loose and extended chain conformation. Moreover, we use light scattering to get the form factor R(g)/R(h) of the PFO solution in which the α-conformation and β-conformation coexist. It is found that R(g)/R(h) increases with the proportion of α-conformation, which indicates that the α-conformation of PFO has a loose and extended chain conformation, and this result agrees well with the conclusions drawn from a and D. On the basis of the fact that the β-conformation (ordered conformation) and α-conformation of PFO can transform into each other in solution, this work is significant for the control of the β-conformation and will have a potential meaning to increase the charge carrier mobility and efficiency from the PFO solution to films.

In this work, the effects of solvation and desolvation on the β phase of poly(9,9-dioctylfluorene) (PFO) are studied. The content of β phase is approximately calculated for comparison. The content of β phase can be enhanced up to 40% by the solvation effect and become a metastable state; the desolvation effect is a dynamic process and can enhance the content of β phase remarkably by 18%age units. It is found that the contents of β phase are always changing with the aggregation degrees of PFO chains. To fully understand it, the concepts of mesoscopic aggregates and macroscopic aggregates are proposed and well proved by the filtration experiment. In the solution (the ethanol content less than 30%), the mesoscopic aggregates are beneficial to enhance the content of β phase; in the solution (the ethanol content more than 40%), which is close to the condensed state of fabricated optoelectronic film, the macroscopic aggregates can make the content of β phase not only much higher but also stable. The content of ...

In this work, the solvent field and temperature are used to explore the mutual transformation dynamic process and mechanism between the α-conformation and β-conformation in poly(9,9-dioctylfluorene) (PFO) precursor solution. The conformational transformation of the PFO chain is researched by UV-vis absorption spectra and the proportions of the β-conformation are quantitatively calculated. The corresponding variation trend of the aggregation structure is researched using a static and dynamic light scattering (SLS/DLS) method. It is found that the mutual transformation processes between the α-conformation and β-conformation are reversible in essence. Especially in the transformation processes, the complicated relationship between the β-conformation and the aggregation structure is understood, that is the aggregation structure promotes formation of the β-conformation under solvent field, then the conformational transformation of the β-conformation promotes the dissociation of the aggregation structure under temperature. The above results give an insight into the β-conformation and the aggregation structure of PFO in theory. Furthermore, under the temperature, we find that both two transformation steps have good linear correlations, which indicates that using temperature can be considered as a good method to accurately control the proportion of β-conformation in actual applications, and it will help us to get the desired proportion of the β-conformation in PFO precursor solution so as to make the charge carrier mobility of optoelectronic films increased and device performance better.