Hydroxypropyl methylcellulose reinforced bilayer hydrogel dressings containing L-arginine-modified polyoxometalate nanoclusters to promote healing of chronic diabetic wounds.

Diabetes-related slow healing of wounds is primarily driven by bacterial infections and angiogenesis disorder and presents a substantial hurdle in clinical treatment. To solve the above problems, an advanced multifunctional hydrogel system based on natural polymer was created here to facilitate wound healing in patients with chronic diabetes. The prepared dressing was composed of an outer hydrogel containing polyvinyl alcohol and hydroxypropyl methyl cellulose in dimethyl sulfoxide and water as binary solvents, and an inner hydrogel containing chitosan quaternary ammonium salt, flaxseed gum, and polyvinyl alcohol. Thus, a polysaccharide based bilayer hydrogel (BH) with superior mechanical strength and biocompatibility was created. This bilayer hydrogel could easily bind to dynamic tissue surfaces, thereby generating a protective barrier. Meanwhile, L-arginine-modified polyoxometalate (POM@L-Arg) nanoclusters were loaded in the inner hydrogel. They released NO when stimulated by the peroxide microenvironment of diabetic wounds. NO as a signal molecule regulated vascular tension and promoted cell proliferation and migration. Additionally, because of the synergistic effect of NO and the chitosan quaternary ammonium salt, the hydrogel system exhibited excellent antibacterial performance. The NO released reduced the levels of proinflammatory factors IL-6 and TNF-α in the diabetic wounds, which thus accelerated wound healing. In short, BH + POM@L-Arg is expected to serve as an ideal wound dressing as it exerts a good promotion effect on diabetes-related wound healing.

Unveiling the agonistic properties of Preyssler-type Polyoxotungstates on purinergic P2 receptors.

The Preyssler-type polyoxotungstate ({P5W30}) belongs to the family of polyanionic metal-oxides formed by group V and VI metal ions, such as V, Mo and W, commonly known as polyoxometalates (POMs). POMs have demonstrated inhibitory effect on a significant number of ATP-binding proteins in vitro. Purinergic P2 receptors, widely expressed in eukaryotic cells, contain extracellularly oriented ATP-binding sites and play many biological roles with health implications. In this work, we use the immortalized mouse hippocampal neuronal HT-22 cells in culture to study the effects of {P5W30} on the cytosolic Ca2+ concentration. Changes in cytosolic Ca2+ concentration were monitored using fluorescence microscopy of HT-22 cells loaded with the fluorescent Ca2+ indicator Fluo3. 31P-Nuclear magnetic resonance measurements of {P5W30} indicate its stability in the medium used for cytosolic Ca2+ measurements for over 30 min. The findings reveal that addition of {P5W30} to the extracellular medium induces a sustained increase of the cytosolic Ca2+ concentration within minutes. This Ca2+ increase is triggered by extracellular Ca2+ entry into the cells and is dose-dependent, with a half-of-effect concentration of 0.25 ± 0.05 µM {P5W30}. In addition, after the {P5W30}-induced cytosolic Ca2+ increase, the transient Ca2+ peak induced by extracellular ATP is reduced up to 100% with an apparent half-of-effect concentration of 0.15 ± 0.05 µM {P5W30}. Activation of metabotropic purinergic P2 receptors affords about 80% contribution to the increase of Fluo3 fluorescence elicited by {P5W30} in HT-22 cells, whereas ionotropic receptors contribute, at most, with 20%. These results suggest that {P5W30} could serve as a novel agonist of purinergic P2 receptors.

Polishing methods for composites restoration: the influence on human gingival fibroblasts behaviour.

BACKGROUND: Carious/Non-carious cervical lesions with gingival recessions may require both dental and periodontal reconstructive therapy, where flaps/grafts may be placed in contact with a dental filling material. Human Gingival Fibroblasts (HGF-1) response during the early phase of healing could vary according to the procedures employed to cure the dental composite. Moreover, oxygen diffusion into dental composite inhibits the polymerization reaction, creating an oxygen-inhibited layer (OIL) that presents residual unreacted monomers. The aim of this study was to assess the effect of different polishing techniques and OIL on HGF-1. METHODS: Composite discs polished with different techniques (diamond rubber, abrasive discs and tungsten carbide burr) were used. An additional not polished smooth group obtained with and without OIL was used as control. Samples were physically characterized through the analysis of their hydrophilicity and surface topography through contact angle measurement and SEM, respectively; afterwards the biologic response of HGF-1 when cultured on the different substrates was analyzed in terms of cytotoxicity and gene expression. RESULTS: The finishing systems caused alterations to the wettability, even if without a proportional relation towards the results of the proliferation essay, from which emerges a greater proliferation on surfaces polished with one-step diamond rubber and with abrasive discs as well as a direct effect of the glycerin layer, confirming that surface roughness can heavily influence the biological response of HGF-1. CONCLUSIONS: Surfaces wettability as well as cellular behavior seem to be affected by the selection of the finishing system used to lastly shape the restoration. Especially, the presence of OIL act as a negative factor in the regards of human gingival fibroblasts. The present study may provide the first clinical instruction regarding the best polishing system of composite material when the restoration is placed directly in contact with soft tissue cells. Understanding HGF-1 behavior can help identifying the polishing treatment for direct restoration of carious/non-carious cervical lesions associated with gingival recessions.

Modulation of cell death mechanisms via α-Ag2WO4 morphology-dependent factors.

The cytotoxic of α-Ag2WO4 synthesized in different morphologies (cuboidal (AW-C), hexagonal rod-like (AW-HRL) and nanometric rod-like (AW-NRL) was analyzed to understand the impact of morphological modulation on the toxicity of 3 T3 cell lines in the dark and when photoactivated by visible light. Pathways of toxicity were examined, such as parameters and electrostatic interaction, uptake, ion release and ROS production. Cytotoxicity was observed for all samples after reaching concentrations exceeding 7.8 µg/mL. Uptake tests demonstrated that the samples were not internalized by cells, likely due to their negative surface charge. AW-NRL exhibited autophagy in the absence of light and during photoactivation, primarily attributed to its ability to generate singlet oxygen. Analyzing intercellular ROS and RNS production, AW-HRL induced an increase in NO through exposure to photo-generated hydroxyl radicals, while AW-NRL showed increases only at non-photoactivated concentrations and AW-C did not exhibit increases. Interestingly, in the dark, these cells showed a low propensity for apoptosis, with late apoptosis and necrosis being more pronounced. When photoactivated, this behavior changed, revealing predominantly apoptotic and late apoptotic cell death. There is a need for an understanding of how morphology can alter the biological properties of α-Ag2WO4 to predict and optimize its effects on cellular responses.

Fabrication of pure Bi2WO6 and Bi2WO6/MWCNTs nanocomposite as potential antibacterial and anticancer agents.

An essential research area for scientists is the development of high-performing, inexpensive, non-toxic antibacterial materials that prevent the transfer of bacteria. In this study, pure Bi2WO6 and Bi2WO6/MWCNTs nanocomposite were prepared by hydrothermal method. A series of characterization results by using XRD FTIR, Raman, FESEM, TEM, and EDS analyses, reveal the formation of orthorhombic nanoflakes Bi2WO6 by the addition of NaOH and pH adjustment to 7. Compared to pure Bi2WO6, the Bi2WO6/MWCNTs nanocomposite exhibited that CNTs are efficiently embedded into the structure of Bi2WO6 which results in charge transfer between metal ion electrons and the conduction or valence band of Bi2WO6 and MWCNTs and result in shifting to longer wavelength as shown in UV-visible and PL. The results confirmed that MWCNTs are stuck to the surface of the microflowers, and some of them embedded inside the Bi2WO6 nanoflakes without affecting the structure of Bi2WO6 nanoflakes as demonstrated by TEM. In addition, Pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite were tested against P. mirabilis and S. mutans., confirming the effect of addition MWCNTs materials had better antibacterial activity in opposition to both bacterial strains than pure Bi2WO6. Besides, pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite tested for cytotoxicity against lung MTT test on Hep-G2 liver cancer cells, and flow-cytometry. Results indicated that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have significant anti-cancer efficacy against Hep-G2 cells in vitro. In addition, the findings demonstrated that Bi2WO6 and Bi2WO6/MWCNTs triggered cell death via increasing ROS. Based on these findings, it appears that pure Bi2WO6 and the Bi2WO6/MWCNTs nanocomposite have the potential to be developed as nanotherapeutics for the treatment of bacterial infections, and liver cancer.

Polyoxometalate exerts broad-spectrum activity against human respiratory viruses hampering viral entry.

Human respiratory viruses have an enormous impact on national health systems, societies, and economy due to the rapid airborne transmission and epidemic spread of such pathogens, while effective specific antiviral drugs to counteract infections are still lacking. Here, we identified two Keggin-type polyoxometalates (POMs), [TiW11CoO40]8- (TiW11Co) and [Ti2PW10O40]7- (Ti2PW10), endowed with broad-spectrum activity against enveloped and non-enveloped human respiratory viruses, i.e., coronavirus (HCoV-OC43), rhinovirus (HRV-A1), respiratory syncytial virus (RSV-A2), and adenovirus (AdV-5). Ti2PW10 showed highly favorable selectivity indexes against all tested viruses (SIs >700), and its antiviral potential was further investigated against human coronaviruses and rhinoviruses. This POM was found to inhibit replication of multiple HCoV and HRV strains, in different cell systems. Ti2PW10 did not affect virus binding or intracellular viral replication, but selectively inhibited the viral entry. Serial passaging of virus in presence of the POM revealed a high barrier to development of Ti2PW10-resistant variants of HRV-A1 or HCoV-OC43. Moreover, Ti2PW10 was able to inhibit HRV-A1 production in a 3D model of the human nasal epithelium and, importantly, the antiviral treatment did not determine cytotoxicity or tissue damage. A mucoadhesive thermosensitive in situ hydrogel formulation for nasal delivery was also developed for Ti2PW10. Overall, good biocompatibility on cell lines and human nasal epithelia, broad-spectrum activity, and absence of antiviral resistance development reveal the potential of Ti2PW10 as an antiviral candidate for the development of a treatment of acute respiratory viral diseases, warranting further studies to identify the specific target/s of the polyanion and assess its clinical potential.

Oxygen-Independent Radiodynamic Therapy: Radiation-Boosted Chemodynamics for Reprogramming the Tumor Immune Environment and Enhancing Antitumor Immune Response.

Radiodynamic therapy (RDT) has emerged as a promising modality for cancer treatment, offering notable advantages such as deep tissue penetration and radiocatalytic generation of oxygen free radicals. However, the oxygen-dependent nature of RDT imposes limitations on its efficacy in hypoxic conditions, particularly in modulating and eliminating radioresistant immune suppression cells. A novel approach involving the creation of a "super" tetrahedron polyoxometalate (POM) cluster, Fe12-POM, has been developed for radiation boosted chemodynamic catalysis to enable oxygen-independent RDT in hypoxic conditions. This nanoscale cluster comprises four P2W15 units functioning as energy antennas, while the Fe3 core serves as an electron receptor and catalytic center. Under X-ray radiation, a metal-to-metal charge transfer phenomenon occurs between P2W15 and the Fe3 core, resulting in the valence transition of Fe3+ to Fe2+ and a remarkable 139-fold increase in hydroxyl radical generation compared to Fe12-POM alone. The rapid generation of hydroxyl radicals, in combination with PD-1 therapy, induces a reprogramming of the immune environment within tumors. This reprogramming is characterized by upregulation of CD80/86, downregulation of CD163 and FAP, as well as the release of interferon-γ and tumor necrosis factor-α. Consequently, the occurrence of abscopal effects is facilitated, leading to significant regression of both local and distant tumors in mice. The development of oxygen-independent RDT represents a promising approach to address cancer recurrence and improve treatment outcomes.

Adaptive Responses of a Peroxidase-like Polyoxometalate-Based Tri-Assembly to Bacterial Microenvironment (BME) Significantly Improved the Anti-Bacterial Effects.

The present study presents the tertiary assembly of a POM, peptide, and biogenic amine, which is a concept to construct new hybrid bio-inorganic materials for antibacterial applications and will help to promote the development of antivirus agents in the future. To achieve this, a Eu-containing polyoxometalate (EuW10) was first co-assembled with a biogenic amine of spermine (Spm), which improved both the luminescence and antibacterial effect of EuW10. Further introduction of a basic peptide from HPV E6, GL-22, induced more extensive enhancements, both of them being attributed to the cooperation and synergistic effects between the constituents, particularly the adaptive responses of assembly to the bacterial microenvironment (BME). Further intrinsic mechanism investigations revealed in detail that the encapsulation of EuW10 in Spm and further GL-22 enhanced the uptake abilities of EuW10 in bacteria, which further improved the ROS generation in BME via the abundant H2O2 involved there and significantly promoted the antibacterial effects.

A Water-Soluble Antimony-Rich Polyoxometalate with Broad-Spectrum Antitumor Activities.

Herein, a giant Sb-rich polyoxometalate (POM) {Sb21 Tb7 W56 } is reported, which contains the largest number of Sb atoms in a POM so far. The Sb-rich POM has many interesting structural features and is a rare example of a soluble and water-stable giant POM. Biomedical studies indicate that the Sb-rich POM exhibits broad-spectrum antitumor activity against various cancer cell lines by reactivating the P53-dependent apoptotic processes and disrupting the mitochondrial membrane. In addition, this Sb-rich POM was capable of suppressing the growth and metastasis of a breast cancer in vivo. This work demonstrates that Sb-rich POMs are promising candidates for the development of new anticancer drugs.

Polyoxometalate Nanoparticles as a Potential Glioblastoma Therapeutic via Lipid-Mediated Cell Death.

Polyoxometalate nanoparticles (POMs) are a class of compounds made up of multiple transition metals linked together using oxygen atoms. POMs commonly include group 6 transition metals, with two of the most common forms using molybdenum and tungsten. POMs are suggested to exhibit antimicrobial effects. In this study, we developed two POM preparations to study anti-cancer activity. We found that Mo-POM (NH4)Mo7O24) and W-POM (H3PW12O40) have anti-cancer effects on glioblastoma cells. Both POMs induced morphological changes marked by membrane swelling and the presence of multinucleated cells that may indicate apoptosis induction along with impaired cell division. We also observed significant increases in lipid oxidation events, suggesting that POMs are redox-active and can catalyze detrimental oxidation events in glioblastoma cells. Here, we present preliminary indications that molybdenum polyoxometalate nanoparticles may act like ferrous iron to catalyze the oxidation of phospholipids. These preliminary results suggest that Mo-POMs (NH4)Mo7O24) and W-POMs (H3PW12O40) may warrant further investigation into their utility as adjunct cancer therapies.

Promising application of polyoxometalates in the treatment of cancer, infectious diseases and Alzheimer's disease.

As shown in studies conducted in recent decades, polyoxometalates (POMs), as inorganic metal oxides, have promising biological activities, including antitumor, anti-infectious and anti-Alzheimer's activities, due to their special structures and properties. However, some side effects impede their clinical applications to a certain extent. Compared with unmodified POMs, POM-based inorganic-organic hybrids and POM-based nanocomposite structures show significantly enhanced bioactivity and reduced side effects. In this review, we introduce the biological activities of POMs and their derivatives and highlight the side effects of POMs on normal cells and organisms and their possible mechanisms of action. We then propose a development direction for overcoming their side effects. POMs are expected to constitute a new generation of inorganic metal drugs for the treatment of cancer, infectious diseases, and Alzheimer's disease.Graphical abstract.

Amelioration of enteric dysbiosis by polyoxotungstates in mice gut.

Here we show that Preyssler-type polyoxotungstates (Preyssler-type POTs, [NaP5W30O110]-14) complexed with peptides can prevent the dysbiotic expansion of anaerobic bacteria of the Enterobacteriaceae family. In a dextran sulfate sodium (DSS)-induced colitis model, symptom remission of C57BL/6 J mice with colitis is achieved by orally treated with POT complexes. Ten days of daily administration of POT complexes reduces 5% body weight loss and the mRNA levels of proinflammatory markers (77% reduction for Il6, 73% reduction for Tnf, 91% reduction for Cxcl1) in the caecum and proximal colon. Bacterial population analysis reveals that these Enterobacteriaceae population in the caecal content decline by one order of magnitude after administration of POT complexes. POT complexes exert anti-inflammatory effects indirectly on the host immune system by inhibition of malignant expansion of anaerobic Enterobacteriaceae during gut inflammation. Furthermore, POTs show negligible effect on bacterial growth in vitro, healthy mice and their microbiota composition under homeostatic conditions. Rationally designed POT complexes will provide distinctive approach to improve enteric bacteria dysbiosis-associated gut inflammation by balancing bacterial communities.

Wells-Dawson phosphotungstates as mushroom tyrosinase inhibitors: a speciation study.

In order to elucidate the active polyoxotungstate (POT) species that inhibit fungal polyphenol oxidase (AbPPO4) in sodium citrate buffer at pH 6.8, four Wells-Dawson phosphotungstates [α/ß-PV2WVI18O62]6- (intact form), [α2-PV2WVI17O61]10- (monolacunary), [PV2WVI15O56]12- (trilacunary) and [H2PV2WVI12O48]12- (hexalacunary) were investigated. The speciation of the POT solutions under the dopachrome assay (50 mM Na-citrate buffer, pH 6.8; L-3,4-dihydroxyphenylalanine as a substrate) conditions were determined by 183W-NMR, 31P-NMR spectroscopy and mass spectrometry. The intact Wells-Dawson POT [α/ß-PV2WVI18O62]6- shows partial (~ 69%) disintegration into the monolacunary [α2-PV2WVI17O61]10- anion with moderate activity (Ki = 9.7 mM). The monolacunary [α2-PV2WVI17O61]10- retains its structural integrity and exhibits the strongest inhibition of AbPPO4 (Ki = 6.5 mM). The trilacunary POT [PV2WVI15O56]12- rearranges to the more stable monolacunary [α2-PV2WVI17O61]10- (~ 62%) accompanied by release of free phosphates and shows the weakest inhibition (Ki = 13.6 mM). The hexalacunary anion [H2PV2WVI12O48]12- undergoes time-dependent hydrolysis resulting in a mixture of [H2PV2WVI12O48]12-, [PV8WVI48O184]40-, [PV2WVI19O69(H2O)]14- and [α2-PV2WVI17O61]10- which together leads to comparable inhibitory activity (Ki = 7.5 mM) after 48 h. For the solutions of [α/ß-PV2WVI18O62]6-, [α2-PV2WVI17O61]10- and [PV2WVI15O56]12- the inhibitory activity is correlated to the degree of their rearrangement to [α2-PV2WVI17O61]10-. The rearrangement of hexalacunary [H2PV2WVI12O48]12- into at least four POTs with a negligible amount of monolacunary anion interferes with the correlation of activity to the degree of their rearrangement to [α2-PV2WVI17O61]10-. The good inhibitory effect of the Wells-Dawson [α2-PV2WVI17O61]10- anion is explained by the low charge density of its protonated forms Hx[α2-PV2WVI17O61](10-x)- (x = 3 or 4) at pH 6.8.

The Preventive Effect of the Phenotype of Tumour-Associated Macrophages, Regulated by CD39, on Colon Cancer in Mice.

BACKGROUND: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. METHODS: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. RESULTS: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. CONCLUSION: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.

{BiW8 O30 } Exerts Antitumor Effect by Triggering Pyroptosis and Upregulating Reactive Oxygen Species.

We successfully synthesized {BiW8 }, a 10-nuclear heteroatom cluster modified {BiW8 O30 }. At 24 h post-incubation, the IC50 values of {BiW8 } against HUVEC, MG63, RD, Hep3B, HepG2, and MCF7 cells were 895.8, 127.3, 344.3, 455.0, 781.3, and 206.3 µM, respectively. The IC50 value of {BiW8 } on the MG63 cells was more than 2-fold lower than that of the other raw materials. Through morphological and functional features, we demonstrated pyroptosis as a newly identified mechanism of cell death induced by {BiW8 }. {BiW8 } increased 2-fold reactive oxygen species (ROS) levels in MG63 cells at 24 h post-incubation. Compared with 0 h, the glutathione (GSH) content decreased by 59, 65, 75, 94, and 97 % at 6, 12, 24, 36 and 48 h post-incubation, respectively. Furthermore, multiple antitumor mechanisms of {BiW8 } were identified via transcriptome analysis and chemical simulation, including activation of pyroptosis, suppression of GSH generation, depletion of GSH, and inhibition of DNA repair.

Polyoxometalates as Effective Nano-inhibitors of Amyloid Aggregation of Pro-inflammatory S100A9 Protein Involved in Neurodegenerative Diseases.

Pro-inflammatory and amyloidogenic S100A9 protein is central to the amyloid-neuroinflammatory cascade in neurodegenerative diseases. Polyoxometalates (POMs) constitute a diverse group of nanomaterials, which showed potency in amyloid inhibition. Here, we have demonstrated that two selected nanosized niobium POMs, Nb10 and TiNb9, can act as potent inhibitors of S100A9 amyloid assembly. Kinetics analysis based on ThT fluorescence experiments showed that addition of either Nb10 or TiNb9 reduces the S100A9 amyloid formation rate and amyloid quantity. Atomic force microscopy imaging demonstrated the complete absence of long S100A9 amyloid fibrils at increasing concentrations of either POM and the presence of only round-shaped and slightly elongated aggregates. Molecular dynamics simulation revealed that both Nb10 and TiNb9 bind to native S100A9 homo-dimer by forming ionic interactions with the positively charged Lys residue-rich patches on the protein surface. The acrylamide quenching of intrinsic fluorescence showed that POM binding does not perturb the Trp 88 environment. The far and near UV circular dichroism revealed no large-scale perturbation of S100A9 secondary and tertiary structures upon POM binding. These indicate that POM binding involves only local conformational changes in the binding sites. By using intrinsic and 8-anilino-1-naphthalene sulfonate fluorescence titration experiments, we found that POMs bind to S100A9 with a Kd of ca. 2.5 µM. We suggest that the region, including Lys 50 to Lys 54 and characterized by high amyloid propensity, could be the key sequences involved in S1009 amyloid self-assembly. The inhibition and complete hindering of S100A9 amyloid pathways may be used in the therapeutic applications targeting the amyloid-neuroinflammatory cascade in neurodegenerative diseases.

CD39-mediated ATP-adenosine signalling promotes hepatic stellate cell activation and alcoholic liver disease.

CD39 is associated with diverse physiological and pathological processes, including cell proliferation and differentiation. Adenosine triphosphate (ATP) is hydrolysed to adenosine by different enzymes including ecto-nucleoside triphosphate diphosphohydrolase-1/ENTPD1 (CD39) and ecto-5'-nucleotidase (CD73), regulating many physiological and pathological processes in various diseases, but these changes and functions in alcoholic liver disease are generally unknown. In this study, an alcoholic liver disease model in vivo was induced by ethanol plus carbon tetrachloride(CCl4) administered to C57BL/6 mice, who were the intraperitoneally injected with the CD39 inhibitor sodium polyoxotungstate (POM1) or colchicine from the 5th week to the 8th week. Meanwhile, hepatic stellate cells were stimulated by acetaldehyde to replicate alcoholic liver fibrosis models in vitro. Exogenous ATP and POM1 were added in turn to the culture system. Pharmacological blockade of CD39 largely prevents liver damage and collagen deposition. We found that blockade or silencing of CD39 prevented acetaldehyde-induced proliferation of HSC-T6 cells and the expression of fibrogenic factors. Moreover, blockade or silencing of CD39 could block the activation of the adenosine A2A and adenosine A2B receptors and the TGF-ß/Smad3 pathway, which are essential events in HSC activation. Thus, blockade of CD39 to inhibit the transduction of ATP to adenosine may prevent HSC activation, alleviating alcoholic hepatic fibrosis. The findings from this study suggest ATP-adenosine signalling is a novel therapeutic and preventive target for alcoholic liver disease.

A supramolecular complex based on a Gd-containing polyoxometalate and food-borne peptide for MRI/CT imaging and NIR-triggered photothermal therapy.

A multifunctional supramolecular complex is reported for the integrated multiple magnetic resonance imaging/computed X-ray tomography (MRI/CT) imaging and photothermal therapy, wherein a gadolinium-substituted paramagnetic polyoxometalate cluster and food-borne antioxidant peptides identified from the trepang protein hydrolysates are introduced. The as-prepared complex maintained an uniform particle size and much better biocompatibility, and is an ideal candidate for the in vivo applications. The complex allows for T1-weighted MR imaging and a high Hounsfield unit value for enhanced CT imaging. Interestingly, we demonstrate that the complex possesses outstanding photothermal cancer-killing effects due to its high photothermal conversion efficiency under the exposure of an NIR laser and enhanced antibacterial activity to avoid bacterial infection from the thermal therapeutic process. These results indicate that the supramolecular complex platform exhibit potential for accurate medical diagnosis at an early stage and effective eradication of the tumor cells.

Bacterial hyperpolarization modulated by polyoxometalates for solutions of antibiotic resistance.

Developing strategies against the antibiotic resistance is a major global challenge for public health. Here, we report the synergy of the combination of Preyssler-type polyoxometalates (POMs) ([NaP5W30O110]14- or [AgP5W30O110]14-) and ribosome-targeting antibiotics for high antibacterial efficiency with low risk of antibiotic resistance. Due to their ultra-small sizes and active surface ligands, POM anions show strong affinity to bacterial cell membrane and impose hyperpolarization of the bacterial cells as well as the decrease of Mg2+ influx by blocking Mg2+ transporters, which finally lead to the structural perturbations of ribosomes and instability of bacterial structures. The bacterial growth can, therefore, be regulated by the presence of POMs: a fraction of Bacillus subtilis shifted to a 'dormant', slow-growing cellular state (an extended lag phase) upon the application of subinhibitory concentration of POMs. An approach to combat antibiotic resistant bacteria by applying POMs at their early growth phase followed by antibiotic exposure is validated, and its high efficiency for bacterial control is confirmed.

Synthesis, characterization and biological evaluation of octyltrimethylammonium tetrathiotungstate.

Octyltrimethylammonium tetrathiotungstate salt (ATT-C8) was synthesized and its ability to chelate copper was evaluated. The biological and toxic aspects were evaluated by in vitro and in vivo assays, using bovine aorta endothelial cells (BAEC) and zebrafish (Danio rerio) embryos. The obtained results suggest that ATT-C8 has better biocompatibility, showing a significantly lower lethal concentration 50 (LC50) value in comparison to ammonium tetrathiotungstate (ATT). Zebrafish embryos assay results indicate that both tetrathiotungstate salts at the studied concentrations increase the hatching time. Even more, an in vivo assay showed that synthesized materials behave as copper antagonists and have the ability to inhibit its toxicological effects. Also, both materials were found to be active for the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The characterization of the materials was carried out using the following spectroscopic techniques: Ultraviolet-Visible (UV-Vis), Fourier Transform Infrared (FTIR) and proton nuclear magnetic resonance (1H-NRM).