Butyrate alleviates alcoholic liver disease-associated inflammation through macrophage regulation and polarization via the HDAC1/miR-155 axis.

BACKGROUND: We recently found that butyrate could ameliorate inflammation of alcoholic liver disease (ALD) in mice. However, the exact mechanism remains incompletely comprehended. Here, we examined the role of butyrate on ALD-associated inflammation through macrophage (Mψ) regulation and polarization using in vivo and in vitro experiments. METHODS: For in vivo experiments, C57BL/6J mice were fed modified Lieber-DeCarli liquid diets supplemented with or without ethanol and sodium butyrate (NaB). After 6 weeks of treatment, mice were euthanized and associated indicators were analyzed. For in vitro experiments, lipopolysaccharide (LPS)-induced inflammatory murine RAW264.7 cells were treated with NaB or miR-155 inhibitor/mimic to verify the anti-inflammatory effect and underlying mechanism. RESULTS: The administration of NaB alleviated pathological damage and associated inflammation, including LPS, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß levels in ALD mice. NaB intervention restored the imbalance of macrophage polarization by inhibiting inducible nitric oxide synthase (iNOS) and elevating arginase-1 (Arg-1). Moreover, NaB reduced histone deacetylase-1 (HDAC1), nuclear factor kappa-B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and miR-155 expression in ALD mice, but also increased peroxisome proliferator-activated receptor-γ (PPAR-γ). Thus, MiR-155 was identified as a strong regulator of ALD. To further penetrate the role of miR-155, LPS-stimulated RAW264.7 cells co-cultured with NaB were treated with the specific inhibitor or mimic. Intriguingly, miR-155 was capable of negatively regulated inflammation with NaB intervention by targeting SOCS1, SHIP1, and IRAK-M genes. CONCLUSION: Butyrate suppresses the inflammation in mice with ALD by regulating macrophage polarization via the HDAC1/miR-155 axis, which may potentially contribute to the novel therapeutic treatment for the disease.

Fullerene Covalent Passivation of Black Phosphorus Nanosheets toward Enhanced Near-Infrared-II Photothermal Therapy.

Photothermal therapy (PTT) triggered by near-infrared-II (NIR-II, 1000-1700 nm) light is developed as a potential tumor therapy technique with deeper tissue penetration capacity and higher allowable laser power density of the skin than NIR-I (750-1000 nm) biowindow. Black phosphorus (BP) with excellent biocompatibility and favorable biodegradability demonstrates promising applications in PTT but suffers from low ambient stability and limited photothermal conversion efficiency (PCE), and utilization of BP in NIR-II PTT is scarcely reported. Herein, we develop novel fullerene covalently modified few-layer BP nanosheets (BPNSs) with ∼9-layer thickness through an easy one-step esterification process (abbreviated BP-ester-C60), bringing about the dramatically enhanced ambient stability of BPNSs due to bonding of the hydrophobic C60 with high stability and the lone electron pair on the phosphorus atom. BP-ester-C60 is then applied as a photosensitizer in NIR-II PTT, delivering a much higher PCE than the pristine BPNSs. Under 1064 nm NIR-II laser irradiation, in vitro and in vivo antitumor studies reveal that BP-ester-C60 exhibits dramatically enhanced PTT efficacy with considerable biosafety relative to the pristine BPNSs. This is interpreted by the boost of NIR light absorption on account of the modulation of the band energy level resulting from intramolecular electron transfer from BPNSs to C60.

Terpenoids: Natural Compounds for Non-Alcoholic Fatty Liver Disease (NAFLD) Therapy.

Natural products have been the most productive source for the development of drugs. Terpenoids are a class of natural active products with a wide range of pharmacological activities and therapeutic effects, which can be used to treat a variety of diseases. Non-alcoholic fatty liver disease (NAFLD), a common metabolic disorder worldwide, results in a health burden and economic problems. A literature search was conducted to obtain information relevant to the treatment of NAFLD with terpenoids using electronic databases, namely PubMed, Web of Science, Science Direct, and Springer, for the period 2011-2021. In total, we found 43 terpenoids used in the treatment of NAFLD. Over a dozen terpenoid compounds of natural origin were classified into five categories according to their structure: monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, and tetraterpenoids. We found that terpenoids play a therapeutic role in NAFLD, mainly by regulating lipid metabolism disorder, insulin resistance, oxidative stress, and inflammation. The AMPK, PPARs, Nrf-2, and SIRT 1 pathways are the main targets for terpenoid treatment. Terpenoids are promising drugs and will potentially create more opportunities for the treatment of NAFLD. However, current studies are restricted to animal and cell experiments, with a lack of clinical research and systematic structure-activity relationship (SAR) studies. In the future, we should further enrich the research on the mechanism of terpenoids, and carry out SAR studies and clinical research, which will increase the likelihood of breakthrough insights in the field.

Boosting Antitumor Sonodynamic Therapy Efficacy of Black Phosphorus via Covalent Functionalization.

Sonodynamic therapy (SDT) triggered by ultrasound represents an emerging tumor therapy approach with minimally invasive treatment featuring nontoxicity and deep tissue-penetration, and its efficacy sensitively depends on the sonosensitizer which determines the generation of reactive oxygen species (ROS). Herein, for the first time covalently functionalized few-layer black phosphorus nanosheets (BPNSs) are applied as novel sonosensitizers in SDT, achieving not only boosted SDT efficacy but also inhibited cytotoxicity relative to the pristine BPNSs. Three different covalently functionalized-BPNSs are synthesized, including the first fullerene-functionalized BPNSs with C60 covalently bonded onto the surface of BPNSs (abbreviated as C60 -s-BP), surface-functionalized BPNSs by benzoic acid (abbreviated as BA-s-BP), and edge-functionalized BPNSs by C60 (abbreviated as C60 -e-BP), and the role of covalent functionalization pattern of BPNSs on its SDT efficacy is systematically investigated. Except C60 -e-BP, both surface-functionalized BPNSs (C60 -s-BP, BA-s-BP) exhibit higher SDT efficacies than the pristine BPNSs, while the highest SDT efficacy is achieved for BA-s-BP due to its strongest capability of generating the hydroxyl (·OH) radicals, which act as the dominant ROS to kill the tumor cells.

Enhancing photoelectrochemical performance of ZnIn2S4 by phosphorus doping for sensitive detection of miRNA-155.

We report the synthesis of phosphorus-doped ZnIn2S4 (ZnIn2S4-xPx) materials through a solid/gas-phase reaction. ZnIn2S4-xPx shows enhanced photoelectrochemical (PEC) performance due to the improved photo-carrier separation efficiency achieved by substituting some of the sulfur with phosphorus. A PEC biosensor was further developed based on ZnIn2S4-xPx, which exhibits excellent analytical performance for miRNA-155.

Antioxidant Activity and Main Chemical Components of a Novel Fermented Tea.

In the present study, we aimed to develop a novel fermented tea (NFT) product and to evaluate their in vitro antioxidant potential and chemical composition. We found that NFT contained a high level of total phenolic compounds (102.98 mg gallic acid equivalents/g extract) and exhibited diverse antioxidant activities, such as scavenging of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and hydroxyl radicals, as well as reducing power. The total catechins in NFT were comparable to those of Lipton black tea (LBT), but lower than those of Boseong green tea (BGT) or Tieguanyin oolong tea (TOT). Among all catechins tested, epigallocatechin (EGC) and epigallocatechin-3-O-gallate (EGCG) were the predominant compounds in NFT. In particular, the contents of total theaflavins (TFs), theaflavin (TF), theaflavin-3-gallate (TF3G), and theaflavin-3'-gallate (TF3'G) in NFT were significantly higher than that of BGT, TOT, or LBT. NFT had the highest level of total essential amino acid and γ-aminobutyric acid (GABA) compared with BGT, TOT and LBT. Furthermore, the sensory evaluation results showed that NFT had satisfactory color, aroma, taste, and overall acceptability scores. Our results highlight the potential usefulness of this novel fermented tea as a nutraceutical food/ingredient with special functional activities.

Dissipation and residues of the diamide insecticide chlorantraniliprole in ginseng ecosystems under different cultivation environments.

Ginseng is a valuable herb, the roots of which have been consumed for medicinal use since ancient times in Asian countries. Currently, its cultivation in China is conducted in either forests or non-forest areas. In this study, we investigated the dissipation and residues of the diamide insecticide chlorantraniliprole (CAP) in ginseng ecosystems in these two cultivation environments. The half-life of CAP in ginseng leaves was calculated to be 16.5 days in non-forest areas and 23.9 days in forests, while the half-life of CAP in the soil under non-forest and forest cultivation was 33.0 and 53.3 days, respectively. The relatively long persistence of CAP in ginseng leaves and soil could be attributed to the unique cultivation techniques of ginseng, which prevents exposure to direct sunlight irradiation and rainfall. The residual amounts of CAP in ginseng leaves, roots, and soil in non-forest areas were 0.168, 0.011, and 0.013 mg kg-1 21 days after CAP application at the maximum label-allowed dosage and frequency versus 0.564, 0.013, and < 0.005 mg kg-1 in forests. CAP application strategies for the control of Lepidoptera pests such as armyworms, and the safety of harvested ginseng roots are recommended for ginseng cultivated in forests and non-forest areas based on the results of the CAP residue experiments.

PB@Au Core-Satellite Multifunctional Nanotheranostics for Magnetic Resonance and Computed Tomography Imaging in Vivo and Synergetic Photothermal and Radiosensitive Therapy.

To integrate multiple diagnostic and therapeutic strategies on a single particle through simple and effective methods is still challenging for nanotheranostics. Herein, we develop multifunctional nanotheranostic PB@Au core-satellite nanoparticles (CSNPs) based on Prussian blue nanoparticles (PBNPs) and gold nanoparticles (AuNPs), which are two kinds of intrinsic theranostic nanomaterials, for magnetic resonance (MR)-computed tomography (CT) imaging and synergistic photothermal and radiosensitive therapy (PTT-RT). PBNPs as cores enable T1- and T2-weighted MR contrast and strong photothermal effect, while AuNPs as satellites offer CT enhancement and radiosensitization. As revealed by both MR and CT imaging, CSNPs realized efficient tumor localization by passively targeted accumulation after intravenous injection. In vivo studies showed that CSNPs resulted in synergistic PTT-RT action to achieve almost entirely suppression of tumor growth without observable recurrence. Moreover, no obvious systemic toxicity of mice confirmed good biocompatibility of CSNPs. These results raise new possibilities for clinical nanotheranostics with multimodal diagnostic and therapeutic coalescent design.

Hydroxysafflor yellow A ameliorates lipopolysaccharide-induced acute lung injury in mice via modulating toll-like receptor 4 signaling pathways.

Hydroxysafflor yellow A (HSYA) is a main bio-active compound important of a traditional Chinese medicine named Carthamus tinctorius L. and has been shown to possess various effects, especially anti-inflammatory benefits and potential protections against acute lung injury (ALI) in previous studies. Therefore, in this present study, we aimed to evaluating effects of HSYA on lipopolysaccharide (LPS)-induced ALI in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results demonstrated that HSYA abated LPS-induced pathological change and attenuated lung vascular permeability and edema. HSYA down-regulated both the ability of myeloperoxidase (MPO) in lung tissues and levels of inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IFN(interferon)-ß in serum. Moreover, HSYA prevented toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and TIR-domain-containing adapter-inducing interferon-ß (TRIF) protein up-expressions. In addition, the activations of mitogen-activated protein kinases including p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) were blocked by HSYA. And also, the phosphorylations of interferon regulatory factor 3 (IRF3), translocation of nuclear factor kappa B (NF-κB)/p65 and inhibitory kappa B (IκB)-α were inhibited by HSYA. In conclusion, HSYA attenuated inflammatory response in ALI mice through inhibition of TLR 4-dependent signaling pathways.

Simultaneous determination of phenolic antioxidants in edible vegetable oils by HPLC-FLD assisted with second-order calibration based on ATLD algorithm.

A novel strategy that combines the chemometrics method with high performance liquid chromatography with fluorescence detector (HPLC-FLD) was developed for the simultaneous determination of seven phenolic antioxidants in six kinds of oil samples. After a simple dilution step, oil samples can be directly injected into the detecting system and the data were measured in a short time with a chromatographic system operating in the gradient elution mode. Since the chromatographic and spectral peaks among interesting analytes and interferences were heavily overlapped, second-order calibration method based on alternating trilinear decomposition (ATLD) algorithm which fully exploiting the second-order advantage was adopted. Successful resolution was obtained in the presence of different matrix interferences in different oil samples, and the developed approach allows the quantification of the antioxidants at levels found in edible vegetable oils, without the necessity of applying either preconcentration or extraction steps, moreover, a column washing is also not required. Meanwhile, the effectiveness and reproducibility of the proposed method were also validated by some statistical parameters like root mean squared error of prediction (RMSEP), limits of detection (LOD) and relative standard deviation (RSD). Then the proposed method was compared with several commonly selected methods in sample preparation, elution time and LOD.

New 23-spirocholestane derivatives from Ypsilandra thibetica.

Three new unusual 23-spirocholestane derivatives, ypsilanogenin (1), ypsilanogenin 3-O-ß-D-glucopyranoside (2), and 4'-acetylypsilanogenin 3-O-ß-D-glucopyranoside (3), were isolated from the whole plants of Ypsilandra thibetica. The structures of compounds 1-3 were deduced by spectroscopic and chemical methods, and the structure of 1 was further confirmed by a single-crystal diffraction analysis. All isolates were evaluated for their inhibitory activities against HIV-1.

Potent anti-HIV activities and mechanisms of action of a pine cone extract from Pinus yunnanensis.

The anti-HIV activities of a pine cone extract (YNS-PY-F) from Pinus yunnanensis have been evaluated, and its mechanisms of action were also explored. The pine cone extract, YNS-PY-F, potently inhibited HIV-1(IIIB), HIV-1(RF), HIV-1(A17), HIV-1(AO18) and HIV-2(ROD) and induced cytopathic effect in C8166 cells with EC50 values of 0.96 µg/mL, 1.53 µg/mL, 0.88 µg/mL, 7.20 µg/mL and 6.17 µg/mL, respectively. The quantification of a p24 production assay showed that YNS-PY-F significantly inhibited the acute replication of HIV-1(IIIB), HIV-1RF, HIV-1(A17) and HIV-1(AO18) in C8166 cells. An MTT assay showed that YNS-PY-F also significantly inhibited the HIV-1(IIIB) induced cytolysis in MT-4 cells with an EC50 value of 2.22 µg/mL. The mechanism assays showed that YNS-PY-F had potent inhibitory effects on the fusion between infected cells and uninfected cells, and the activity of HIV-1 reverse transcriptase, with EC50 values of 7.60 µg/mL and 4.60 µg/mL, respectively. Overall, these data suggest that the pine cone extract from Pinus yunnanensis has potent inhibitory activities against HIV-1(IIIB), HIV-1(RF), RT inhibitor-resistant strains HIV-1(A17) and HIV-1(AO18), and HIV-2(ROD), and its anti-HIV mechanisms include inhibition of HIV entry and inhibition of reverse transcriptase activity.