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Lentinan is a natural β–glucan with various bioactivities and is combined with chemotherapy drugs for cancer treatment. Regorafenib is an oral multi-kinase inhibitor approved by FDA for treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors. Regorafenib has poor water solubility and multiple toxicities. We report drug–drug nanosuspensions of regorafenib and lentinan. Results of dynamic light scattering and scanning electron microscopy showed that the mean particle size of the regorafenib–lentinan nanosuspensions was approximately 200 nm and was uniformly distributed. Transmission electron microscopy findings indicated that lentinan stabilized the nanosuspensions by steric manner. Hydrogen bonds and hydrophobic interactions were found between regorafenib and lentinan by molecular dynamics simulation. The results of cytotoxicity assay and pharmacokinetics study in rats showed that the regorafenib–lentinan nanosuspensions reduced the toxicity and enhanced the in vitro anticancer activity and oral bioavailability of regorafenib. Lentinan as a natural stabilizer has the potential using for drug nanosuspensions. Drug–drug nanosuspensions are a new form of combination therapies that can reduce the number of drugs taken by patients and improve their compliance.

Hemoperfusion has become the third-generation treatment strategy for patients suffering from hyperbilirubinemia, but adsorbents used for bilirubin removal mostly face intractable problems, such as unsatisfactory adsorption performance and poor hemocompatibility. Metal–organic frameworks (MOFs) are promising adsorbents for hemoperfusion due to their high specific surface areas and easily modified organic ligands. However, their microporous properties and separation have hampered their application. Here, a novel hierarchical core–shell nanoplatform (named Double-PEG) with tailored binding sites and pore sizes based on Fe3O4@C and Uio66-NH2 was constructed. Notably, Double-PEG showed excellent bilirubin uptake of up to 1738.30 mg g−1 and maintained excellent bilirubin removal efficiency in simulated biological solutions. A study on the adsorption mechanism showed that the adsorption of Double-PEG towards bilirubin tended to be chemical adsorption and in accordance with the Langmuir model. Besides, the good separability, recyclability, cytotoxicity and hemocompatibility of Double-PEG show great potential in hemoperfusion therapy. The finding of this study may provide a novel insight into the application of MOF materials in the field of hemoperfusion.

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs) that pose serious challenges to aquatic animals and environments. Compared with BDE-47 which was one of the most toxic congeners known to date, BDE-209 is less toxic with higher abundance in biotic and abiotic samples. In this study, we have explored the effects of BDE-47 and BDE-209 at different concentrations on the radical oxygen species (ROS) levels and the antioxidant defense system of Brachionus plicatilis. Antioxidant indexes were measured, including total protein content (TSP), the activities of antioxidant enzymes, lipid peroxidation and DNA damage. The results indicated that while low concentrations of PBDEs could activate the antioxidant defense mechanisms, prolonged exposure to higher concentrations of PBDEs could impair the antioxidative capacity of B.plicatilis (P 0.05). The overwhelming of the B.plicatilis antioxidant defense mechanism led to an accumulation of free radicals, resulting in the overactivation of lipid peroxidation and the increased frequency of DNA damage (P 0.05). By studying the toxicity of PBDEs and the detoxification mechanism of B.plicatilis, our research has revealed useful indexes for detecting and monitoring the level of BDE-47 and BDE-209 in the future. Altogether, this study holds immense value in the field of ecotoxicology and environmental safety and will aid in the proper management of PBDEs pollution.

Folliculitis decalvans (FD) is a rare, chronic primary scarring alopecia that classically presents with perifollicular pustules, scaling, crusting, and tufted hair in the affected areas of the scalp, accompanied by pruritus or pain.1 The cause of FD remains unclear; however, on histopathology, it presents as a predominantly neutrophilic inflammatory process targeting hair follicles, resulting in irreversible damage and permanent hair loss.1 Currently, there is no cure for FD. Most treatment regimens are directed at controlling the scalp-associated microbes with antibiotics and antiseptics, managing the inflammation, and preventing further hair loss with immunomodulators.2 Recent case reports have suggested that autologous platelet-rich plasma (PRP) can be a promising adjunct therapy for the treatment of lymphocytic scarring alopecia.3,4 However, there are no data on the efficacy of PRP in neutrophilic scarring alopecias, such as FD. Here, we present 2 patients with long-standing, refractory FD who experienced stability in hair loss and significant symptomatic improvement in inflammation with concurrent PRP treatments. The severity of scalp inflammation was graded (Table I) by a single dermatologist (NAM) during each clinical visit. Table I Grading scale of disease severity

HER2+ breast cancer is highly aggressive and proliferative even after multiple chemotherapy regimens. At present, the available clinical treatment duration of chemotherapeutic agents is limited by severe toxicity to noncancerous tissues, which are attributed to insufficient targeting. Here, we designed an active-targeted and pH-responsive liposome to improve the treatment. The ideas were as follows: (1) using liposome as a nano-delivery system for HER2 inhibitor (lapatinib; LAP) to reduce the toxicity; (2) modifying the capsule with T7 peptide for specific targeted delivery to the tumor cells, and (3) enabling the capsule with the pH-sensitive ability and triggering sustained drug release at extracellular weakly acidic microenvironment to emerge toxicity in tumors and to improve curative effects. It was found that T7 peptide-modified pH-sensitive liposome (T7-LP) was more effective and safer than free drug and unmodified liposome, and reduced drug-induced side effects and noncancerous toxicity. These results support the application potential of T7-LP in improving the efficacy of LAP in HER2+ breast cancer treatment. It might be a novel LAP formulation as a clinical agent.

The contamination of the surface and groundwaters by estrogens and metals poses considerable threat to environment and public health. Herein, we reported a Zr(IV)-cross-linked carboxymethyl-β-cyclodextrin (Zr/CM-β-CD) bifunctional adsorbent, which was constructed by a simple, versatile, and green method through the chelation reaction between CD carboxyl and Zr(IV), to simultaneously remove estrogens and metals from aqueous solution. In this system, the CD cavities encapsulated estrogen micropollutants through the host/guest interactions, and the residual carboxyl groups were expected to act as chelating sites for metal ions. In the monocomponent system, the maximum adsorption capacities of Zr/CM-β-CD adsorbent toward the estrogens estradiol and bisphenol A and metals Cd(II) and Cu(II) were 210.53, 182.15, 118.34, and 78.80 mg/g, respectively. Langmuir isothermal model was suitable to describe the adsorption process, and the adsorption mechanism was further verified through solid-state 13C NMR, FT-IR, and EDS. The adsorption capacities of the adsorbent were maintained at high levels after five cycles. Most importantly, the Zr/CM-β-CD adsorbent was highly efficient in the simultaneous uptake of estrogen and metal pollutants. Thus, the advantages of simple and green fabrication, excellent adsorption capacity, and perfect regenerate ability demonstrated that the Zr/CM-β-CD adsorbent possessed potential for application in the treatment of environmental pollution. This study also provides a new insight into the preparation of the advanced trifunctional CD polymer absorbent under simple and green conditions for water purification.

In the liver, Wnt/β-catenin signaling is involved in regulating zonation and hepatocyte proliferation during homeostasis. We examined Wnt gene expression and signaling after injury, and we show by in situ hybridization that Wnts are activated by acute carbon tetrachloride (CCl4 ) toxicity. Following injury, peri-injury hepatocytes become Wnt-responsive, expressing the Wnt target gene axis inhibition protein 2 (Axin2). Lineage tracing of peri-injury Axin2+ hepatocytes shows that during recovery the injured parenchyma becomes repopulated and repaired by Axin2+ descendants. Using single-cell RNA sequencing, we show that endothelial cells are the major source of Wnts following acute CCl4 toxicity. Induced loss of β-catenin in peri-injury hepatocytes results in delayed repair and ultimately injury-induced lethality, while loss of Wnt production from endothelial cells leads to a delay in the proliferative response after injury. Conclusion: Our findings highlight the importance of the Wnt/β-catenin signaling pathway in restoring tissue integrity following acute liver toxicity and establish a role of endothelial cells as an important Wnt-producing regulator of liver tissue repair following localized liver injury.

Hemoperfusion has become the third-generation treatment strategy for patients suffering from hyperbilirubinemia, but adsorbents used for bilirubin removal mostly face intractable problems, such as unsatisfactory adsorption performance and poor hemocompatibility. Metal-organic frameworks (MOFs) are promising adsorbents for hemoperfusion due to their high specific surface areas and easily modified organic ligands. However, their microporous properties and separation have hampered their application. Here, a novel hierarchical core-shell nanoplatform (named Double-PEG) with tailored binding sites and pore sizes based on Fe3O4@C and Uio66-NH2 was constructed. Notably, Double-PEG showed excellent bilirubin uptake of up to 1738.30 mg g-1 and maintained excellent bilirubin removal efficiency in simulated biological solutions. A study on the adsorption mechanism showed that the adsorption of Double-PEG towards bilirubin tended to be chemical adsorption and in accordance with the Langmuir model. Besides, the good separability, recyclability, cytotoxicity and hemocompatibility of Double-PEG show great potential in hemoperfusion therapy. The finding of this study may provide a novel insight into the application of MOF materials in the field of hemoperfusion.

The clinical efficacy of lenvatinib (LFT) is limited by its poor aqueous solubility and low bioavailability. In this work, LFT-loaded soy phospholipid and sodium glycocholate mixed micelles (LFT-MMs) were prepared through classical co-precipitation. And it was served as an oral administration to address these shortcomings. The preparation conditions were optimized by single-factor experiments. The mass ratio of PC, SGC and LFT, and the species of dispersing media were proved to be decisive factors in controlling the properties of LFT-MMs. The optimal LFT-MMs presented prominent enhancement (500-fold) in LFT solubility, high encapsulation efficiency (87.6 %) as well as suitable stability (>1 month at 4 °C). The biocompatibility of LFT-MMs was estimated by in vitro serum stability measurement and hemolysis test. It showed that serum proteins hardly adhered to the surface of LFT-MMs, and insignificant hemolytic rate (

As a new form of nicotine introduction for novel tobacco products, the interaction of nicotine salt with biological macromolecules may differ from that of free nicotine and thus affect its transport and distribution in vivo. Hence, the mechanism underlying the interaction between 2,6-dihydroxybenzoic acid nicotine salt (DBN) and human serum albumin (HSA) was investigated by multi-spectroscopy, molecular docking, and dynamic simulation. Experiments on steady-state fluorescence and fluorescence lifetime revealed that the quenching mechanism of DBN and HSA was dynamic quenching, and binding constant was in the order of 10^4 L mol

It is promising to fabricate renewable and flexible electronic devices due to increasing awareness of sustainable development of environmental-friendly materials. Flexible and renewable bio-based composite film (GLFF) based on graphene and lotus fiber (LF) was prepared by adding graphene into the mixture solution of lotus fiber and ionic liquid. The GLFFs show high electrical conductivity, remarkable electrochemical performance, excellent electromagnetic interference (EMI) shielding effectiveness (SE) and ability to generate heat. The surface resistance of GLFF reaches 19.01 Ω sq−1. The EMI SE of GLFF arrives at 30 dB at the frequency ranging from 1 to 18 GHz. In addition, the surface temperature of GLFF reaches 46.5 °C when only 7 V was applied on GLFF surface. The area capacitance of the GLFF is 1088.7 mF cm−2. GLFF can maintain a specific capacitance of 85% of initial capacitance after 500 cycles. The influences of graphene content on mechanical property, sheet resistance, heat generation, EMI SE and electrochemical performance of GLFFs were investigated. GLFF, as renewable electrical materials, can be potentially applied in the fields of energy storage, electromagnetic shielding and heat generation.

Dabrafenib is a novel targeted antimelanoma drug. The present work explored the binding mechanism of dabrafenib-human serum albumin (HSA) and the effect on the esterase-like activity and antioxidant activity of HSA by using 19F NMR, spectroscopy methods, and molecular dynamics simulation. The results of 19F NMR, fluorescence, and time-resolved fluorescence spectroscopy revealed that dabrafenib spontaneously binds to the subdomain IIIA of the HSA by hydrophobic action and forms a static complex. The binding affects the esterase-like activity of HSA but not its antioxidant activity. According to the results of molecular dynamics simulation, dabrafenib interacts with Arg410 and Tyr411, which are the key residue associated with the esterase-like activity of HSA. Meanwhile, dabrafenib does not interact with Cys34, the key residue associated with the antioxidant activity of HSA. The results of circular dichroism spectroscopy and molecular dynamics simulation show that the conformation of HSA is not affected by the binding of dabrafenib. This study can provide useful information for understanding the pharmacokinetic properties of dabrafenib.

This study aimed to develop a novel sustained release system for mesalazine (MSZ) by preparing hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex loaded chitosan (CS) nanoparticles (NPs). The HP-β-CD/MSZ complex was prepared at 1:1 stoichiometry and characterized by using various analysis techniques. The HP-β-CD/MSZ/CS NPs prepared under the optimum condition had a spherical shape (90±17 nm diameter), a narrow size distribution, and a high loading efficiency. Compared with free MSZ, the HP-β-CD/MSZ/CS NPs exhibited an obvious sustained release of MSZ. The activity of the NPs against a cytokine-triggered inflammatory response was evaluated in cytokine-stimulated HT-29 cell lines by monitoring key inflammatory mediators. The results revealed that compared with free MSZ, the NPs more strongly inhibited the production of NO, PGE2, and IL-8, indicating the NPs possibly had better anti-inflammatory effects. Therefore, the established HP-β-CD/MSZ/CS NPs may be a promising delivery system of MSZ.

This work aims to explore the inclusion mechanism and structure of cinnamaldehyde (CNMA) and cyclodextrins (CDs), and to provide some theoretical information for the application of CNMA and its inclusion. In this study, we prepared three kinds of inclusion and investigated the mechanism and structure by theory and experiment. Molecular docking and dynamical simulations presented a stable 1:1 inclusion complex and the visual structure model. The structural features indicated that the benzene ring of CNMA was enclosed in the hydrophobic cavity of CDs, which were consistent with the results of 1H NMR, 2D-ROESY, Fourier transform infrared spectroscopy. The inclusion mechanism studies showed that the inclusion process was driven mainly by enthalpy with the binding constant following the order of DM (dimethyl) > HP (hydroxypropyl) > β-CD. Moreover, the inclusion complex showed an advantageous water solubility and dissolution rate compared with CNMA.

The interaction mechanism and binding mode of capecitabine with ctDNA was extensively investigated using docking and molecular dynamics simulations, fluorescence and circular dichroism (CD) spectroscopy, DNA thermal denaturation studies, and viscosity measurements. The possible binding mode and acting forces on the combination between capecitabine and DNA had been predicted through molecular simulation. Results indicated that capecitabine could relatively locate stably in the G-C base-pairs-rich DNA minor groove by hydrogen bond and several weaker nonbonding forces. Fluorescence spectroscopy and fluorescence lifetime measurements confirmed that the quenching was static caused by ground state complex formation. This phenomenon indicated the formation of a complex between capecitabine and ctDNA. Fluorescence data showed that the binding constants of the complex were approximately 2 × 10

In this study, a visible-light-driven photocatalyst Bi2WO6/TiO2 composite was reported using one-step hydrothermal method and then coated on the polyester fabric. The samples were systematically characterized by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area, UV–vis diffuse reflection spectroscopy and photoluminescence spectroscopy (PL). The photocatalytic activity of Bi2WO6/TiO2 coated polyester fabric was evaluated by degradation of Rhodamine B (RhB) and Methylene blue (MB) under visible light irradiation. The self-cleaning property of the fabrics was assessed through removing red wine stain. The results reveal that the Bi2WO6/TiO2 composites with irregular shape are coated on the polyester fabric successfully. The UV–vis absorption spectra show a broad absorption band in the visible region, which extends the scope of absorption spectrum and helps to improve the photocatalytic degradation efficiency. Photocatalytic activities of the Bi2WO6/TiO2 composite polyester fabric are associated with the content of TiO2. Bi2WO6/15%TiO2 coated polyester fabric exhibits the degradation efficiency for RhB and MB up to 98% and 95.1%, respectively, which is much higher than that of pure Bi2WO6 and TiO2 coated polyester fabric. Moreover, Bi2WO6/15%TiO2 coated polyester fabric shows good cycle stability toward continuous three cycles of photocatalytic experiment for dyes degradation. In addition, the Bi2WO6/TiO2 coated polyester fabric shows good self-cleaning property. This work could be extended to design of other composite photocatalyst coating on the fabric for enhancing activity by coupling suitable wide and narrow band-gap semiconductors.

Lotus stems were treated with sodium hydroxide followed by sodium chlorite to prepare lotus fibers. The lotus fibers were characterized by scanning electron microscopy (SEM), Fourier transform infr...

Bismuth tungstate/lotus fiber composite membrane (Bi2WO6/LF) were prepared. The composite membranes were characterized by scanning electron microscopy (SEM), energy dispersive spectrum (EDS) and X-ray diffraction (XRD). The photocatalytic activity of Bi2WO6/LF under visible light irradiation was investigated. The result shows that photocatalytic activity of the Bi2WO6/LF increase with the rise of Bi2WO6 content in the composite membrane. Bi2WO6/LF with 1% Bi2WO6 possesses excellent photocatalytic activity for methylene blue and degradation efficiency of methylene blue reach 94% after irradiation for 270 min. Bi2WO6/LF could be potentially applied in sewage disposal and environmental remediation.

Bi2WO6 particles were prepared and then coated on the polyester fabric. Surface morphology, crystal structure, and chemical structure of the Bi2WO6 particle coated polyester fabric were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Photocatalytic activity was evaluated by the degradation of methylene blue (MB) under ultraviolet light irradiation. Influences of the different concentrations of Bi2WO6 on the deposit weight and the photocatalytic activity of the Bi2WO6 particle coated polyester fabric were investigated. In addition, UV protection of the Bi2WO6 particle coated polyester fabric was examined. The results show that Bi2WO6 particles are uniformly coated on the surface of the polyester fabric. The Bi2WO6 particles coated on the polyester fabric are irregular and are orthorhombic. In addition, the Bi2WO6 particle coated polyester fabric exhibits excellent photocatalytic activity and UV protection. The average degradation efficiency of MB in the presence of the Bi2WO6 particle on the polyester fabric coated with 10 g/l Bi2WO6 reaches 98.6 % after being illuminated for 7 h. Therefore, the Bi2WO6 particle coated polyester fabric shows excellent photocatalytic stability for dyes degradation.

In this study, a visible-light-driven photocatalyst Bi2WO6 was assembled on fibers by linking of poly(diallyldimethylammonium chloride) (PDDA) at room temperature. The samples were characterized by scanning electron microscopy, energy-dispersive spectroscopy and X-ray diffraction. Photocatalytic activity was evaluated by degradation of Rhodamine B (RhB) and Acid orange 7 (AO7) under visible light irradiation. Effects of concentration of PDDA in the pretreatment solution on degradation efficiency of RhB and AO7 in the presence of Bi2WO6 coated cotton fabrics were investigated. In addition, washing durability and breaking strength of Bi2WO6 coated cotton fabrics modified with PDDA were examined. The results revealed that Bi2WO6 with irregular shape were successfully coated on the cotton fabric modified with PDDA. Bi2WO6 coated cotton fabric modified with PDDA exhibited excellent photocatalytic activity with degradation efficiency of 97.4% of RhB and 94.5% of AO7, respectively. In addition, Bi2WO6 coating on the cotton fabrics modified with PDDA not only improved washing durability but also enhanced breaking strength of the fabric.

Lotus fibers were prepared from lotus stems through being treated with sodium hydroxide. The lotus fibers were characterized by scanning electron microscopy (SEM), fourier transform infrared spectrometry (FTIR), X-ray diffraction (XRD) and thermal analysis (TG and DTA). The results indicate that the length of lotus fibers ranges from 3.52 cm to 5.80 cm and the width of lotus fibers ranges from 50 μm to 90 μm. Lotus fibers belong to celluloses fiber with cellulose I structure and the crystallinity of lotus fibers is 48.50 %. The lotus fibers consist of cellulose, lignin, hemicellulose, pectin, lipid and water-soluble substances. The effect of concentration of sodium hydroxide, time and temperature of treatment on removal of impurities, fineness and breaking strength of lotus fibers were investigated. The results suggest that the removal of impurities and breaking strength increase with the rise of concentration of the sodium hydroxide, time and temperature of treatment, respectively. However, the fineness of lotus fibers decreases with an increase in concentration of the sodium hydroxide, time and temperature of treatment. The results are expected to provide valuable guidance for preparation of lotus fibers through simple treatment with sodium hydroxide, which can be applied in textile industry.

Bi 2 WO 6 particles were grown onto the polyester fabric modified with dopamine through a facile dip-coating method. The chemical composition, surface morphology and crystal structure of the Bi 2 WO 6 coated polyester fabric modified with dopamine were characterized by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The photocatalytic activity was evaluated by the degradation of methylene blue (MB) and acid orange 7 (AO7) under visible light irradiation. The influences of dopamine concentrations on the degradation efficiency of MB and AO7 were investigated. Optical absorptions of the Bi 2 WO 6 coated polyester fabric modified with dopamine before and after degrading the dyes were studied. Adhesive strength between the Bi 2 WO 6 coating and the polyester fabric modified with dopamine was evaluated. The tensile strength of the Bi 2 WO 6 coated polyester fabric modified with dopamine was also examined. The results show that the Bi 2 WO 6 particles are uniformly coated on the surface of the polyester fabric modified with dopamine. The Bi 2 WO 6 coated polyester fabric modified with dopamine exhibits excellent photocatalytic activity with degradation efficiency of 97.7% of MB and 96.8% of AO7, respectively. The largest degradation efficiency is obtained when concentration of dopamine is 3 g/L. In addition, the Bi 2 WO 6 coating and the polyester fabrics modified with dopamine not only improve the adhesive strength but also improve the breaking strength.

The interaction of synthetic azo dye Acid Red 14 with pepsin was studied by fluorescence spectroscopy, UV-vis spectroscopy, circular dichroism and molecular docking. Results from the fluorescence spectroscopy show that Acid Red 14 has a strong capability to quench the intrinsic fluorescence of pepsin with static quenching. Binding constant, number of the binding sites and thermodynamic parameters were measured at different temperatures. The result indicates that Acid Red 14 interact with pepsin spontaneously by hydrogen bonding and van der Waals interactions. Three-dimensional fluorescence spectra and circular dichroism spectra reveal that Acid Red 14 could slightly change the structure of pepsin. The hydrogen bond is formed between Acid Red 14 and Tyr-189 and Thr-218 residues of pepsin. Furthermore, the binding between Acid Red 14 and pepsin inhibits pepsin activity. The study can provide a way to analyze the biological safety of Acid Red 14 on digestive proteases or other proteins.

The presence of dyes in a water system has potential adverse effects on the ecological environment. The conventional cyclodextrin (CD) polymer only has CD cavities as adsorption sites and exhibits slow adsorption for dye removal. In this study, we designed a novel carboxymethyl β-CD polymer (β-CDP-COOH). The structural properties of β-CDP-COOH were characterized as an irregular cross-linked polymer with negative surface charge, and the introduction of carboxymethyl groups greatly enhanced the adsorption ability of the β-CD polymer to basic fuchsin (BF). The maximum removal efficiency of β-CDP-COOH (96%) could be achieved within 1 min, whereas that of conventional β-CD polymer (70%) was achieved after 50 min. The adsorption mechanism revealed that the adsorption behavior of β-CDP-COOH could be effectively fitted with the pseudo-second-order kinetic model and Langmuir isotherm. Both CD cavities and carboxymethyl groups were effective adsorption sites, so β-CDP-COOH had an advantage in adsorption capacity over the conventional β-CD polymer. This study indicated that β-CDP-COOH is a potential highly efficient adsorbent for the removal of cationic dye contaminants.

The objective of present study is to explore whether polysaccharide could be a crystal growth inhibitor in poorly soluble antitumor drug Ibrutinib (IBR) formulation. In this work, small molecular ligands (amino or organic acids) in co-amorphous system (CAS) were preliminarily screened. A polysaccharide, microcrystalline cellulose (MCC) was selected to stabilize amorphous drug and enhance pharmacokinetic properties. Fourier-transform infrared, Raman, and X-ray photoelectron spectroscopy confirmed the ionic interaction of the ternary IBR formulation. Moreover, the biosafety of the ternary formulation was the same as that of IBR while the in vitro performance advantage of the ternary formulation was converted into higher bioavailability in vivo experiments. Overall, MCC as an effective crystal growth inhibitor in the novel ternary IBR formulation is a promising approach to improve the dissolution rate of crystalline drugs and the stability of amorphous drugs, as well as providing a theoretical basis for clinical applications.

The study mainly aimed to improve the aqueous solubility of Balofloxacin (BLFX) by preparing the inclusion complexes (ICs) of BLFX with cyclodextrins (CDs). In this study, ICs in solid state were obtained by using beta-CD (β-CD), 2-hydroxypropyl-β-CD (HP-β-CD), 2, 6-dimethyl-β-CD (DM-β-CD) through a freeze-drying technique. The formation of ICs was confirmed through Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, nuclear magnetic resonance, and scanning electron microscopy. Results demonstrated that the water solubility and dissolution rates of three ICs were distinctly improved than that of parent BLFX. Bacteriostatic experiment manifested that the antibacterial effect of BLFX was not inhibited after encapsulation in CDs. The damage of BLFX to kidney and liver cells was reduced. Consequently, successful preparation of the ICs of BLFX with CDs provided possibility for devising new dosage form of BLFX, which held great promise for further applications in clinical fields.

Empagliflozin is an oral sodium glucose co-transporter-2 inhibitor for type 2 diabetes mellitus. The interaction between empagliflozin and human serum albumin (HSA) was investigated experimentally and theoretically. Fluorescence quenching and time-resolved fluorescence spectroscopy indicated that the quenching mechanism of empagliflozin and HSA was dynamic and that the effective binding constant at body temperature was 3.495 × 10

Nanoscale metal-organic frameworks (NMOFs) have attracted considerable attention for controlled drug delivery. However, the interaction between nanoparticles and the biological macromolecules of physiological system must be valued because the formed protein corona will endow NMOFs with new biorecognition properties. In this study, we carried out detailed protein adsorption studies in vitro and cell uptake tests of HeLa cells for nanospherical Uio66 and nanooctahedral Uio67. Uio67 with higher binding constants to human serum albumin needed to combine more protein molecules to achieve colloidal stability state than that needed by Uio66, and this phenomenon led Uio67 to aggregate under the same incubation condition due to the formation of a single-layer protein. Uio67 also induced an evident conformation change in protein to stabilize the combination. In particular, the cell uptake efficiencies of the two systems showed a significant thickness dependence on the protein corona. When samples incubated in 10% fetal bovine serum (FBS), the intracellular rate was the highest for both systems, but the rate was not proportional to the FBS concentration. Results of this work are important to the development of the considerable potential NMOFs-based medicals and also provide additional insight into protein corona.

In this study, a novel Bruton’s tyrosine kinase inhibitor, ibrutinib, was loaded into chitosan/sulfobutylether-β-cyclodextrin nanoparticles (NPs). NPs have gained high loading efficiency for the hydrophobic drug due to the inclusion of cyclodextrin. Ibrutinib-loaded NPs with an average diameter of 277.9 nm and ζ-potential of +19.1 mV were obtained after regulating several influencing factors. Electrostatic reaction between mucin and NPs indicated that the NPs had a mucoadhesive property. Kinase catalytic phosphorylation was monitored by capillary zone electrophoresis and found that chitosan/sulfobutylether-β-cyclodextrin NPs did not weaken ibrutinib activity on the target kinase. In vitro drug release studies revealed that ibrutinib-loaded NPs exhibited a significantly slower gastric-release rate. This study applied a feasible nanocarrier for ibrutinib delivery, and the potential nanoformulation maintains drug activity and shows a sustained release property. These outcomes are helpful for the formulation exploitation of tyrosine kinase inhibitors.

Introduction of hydrophilic groups can improve the solubility of leading drugs but inevitably affect their interaction with proteins. This study selected sirtuin inhibitors Tenovin-1 (T1) and Tenovin-6 (T6) as drug models to determine differences in binding mode to human serum albumin (HSA). T1 and T6 quenched the endogenous fluorescence of HSA via static quenching mechanism. Introduction of hydrophilic groups greatly reduced the binding constant, i.e., from 1.302 × 104 L mol−1 for the HSA-T6 system to 0.128 × 104 L mol−1 for the HSA-T1 system. HSA-T1 system was mainly driven by electrostatic interactions while that of HSA-T6 system was hydrophobic interaction and both systems were spontaneous reactions. Site marker experiments and molecular docking indicated that both systems mainly bound to the hydrophobic site I of HSA. Molecular dynamics (MD) simulation analysis further revealed that Tyr148, Tyr150 and Arg257 residues played a key role in this recognition process for both systems. In particular, T6 maintained additional several hydrogen bonds with the surrounding residues. T1 had almost no effect on the esterase-like activity of HSA, but T6 inhibited the hydrolysis of p-NPA. Furthermore, differential scanning calorimetry (VP-DSC), circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy confirmed that HSA in the T6 system undergone a more significant conformational transition than that in the T1 system.

In this study, 2,2′-(4,4′-biphenylylenebisvinylene)bisbenzenesulfonicacid (CBS-X) and its disodiumsalt (CBS) were used as model compounds to investigate the interaction mechanism between 4,4′-distyrylbiphenyl based fluorescent whitening agents (DSBP-FWAs) and human serum albumin (HSA) through various techniques, including 1H saturation transfer difference nuclear magnetic resonance (1H STD-NMR), fluorescence studies, UV-vis absorption, Fourier transform infrared (FT-IR) spectroscopy, circular dichroism (CD) spectroscopy, and molecular docking. The 1H STD-NMR analyses indicated that CBS and CBS-X can bind to HSA at the favored Sudlow's sites II and I, respectively. Fluorescence emission spectra showed that CBS and CBS-X quenches HSA fluorescence through a dynamic mechanism, and this was further verified by fluorescence lifetime experiments and UV-vis absorption. Moreover, the effective binding constant values of the two compounds at the same temperature decreased in the order CBS > CBS-X. Furthermore, the energy transfer efficiency for CBS and CBS-X were 50.5% and 40.6%, respectively. Thermodynamic analyses indicated that the binding of CBS and CBS-X with HSA are both primarily controlled by hydrophobic forces. FT-IR and CD spectroscopy provided complementary information on the micro-environmental and conformational changes of HSA with the additions of CBS and CBS-X. Molecular docking further confirmed the NMR and spectroscopic results. Overall, the comparative studies on the interaction mechanism of CBS and CBS-X when binding to HSA may provide useful information for evaluating their effects on the human body.

This project aimed to explore the inclusion mechanism and structure of azo dye ethyl red (ER) included into cyclodextrins (CDs) through experiments and computer simulation. Molecular docking and dynamic simulations presented a stable 1:1 inclusion complex and the visual structure model that the ethyl end of ER was enclosed into the cavity of CDs, which were consistent with the results of Job plots, 1H NMR and 2D-ROESY. The inclusion process driven mainly by entropy with the binding constant following the order of DM (dimethyl)-β-CD > HP (hydroxypropyl)-β-CD. The aqueous solubility of ER was significantly improved by the inclusion of CDs.

Drug polymer carriers usually have good sustained release character. In this study, epichlorohydrin was used as cross-linking agent for synthesizing the beta-cyclodextrin polymer microspheres (β-CDPM) by adopting the method of inverse emulsion polymerization. The scanning electron microscope, infrared spectra, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric, 1H NMR and solid state nuclear magnetic resonance were utilized to characterize the structure, surface morphology, thermal stability and crystallinity of the obtained β-CDPM. In vitro release experiment of ornidazole-β-CDPM under preferred experimental condition was studied and the cumulative release curves at different pH values were obtained. The drug loading rate of β-CDPM is 8.86% under preferred process. The release time of the synthesized microspheres was 9 h, which showed good sustained-release behavior. Antibacterial test result indicated that β-CDPM did not affect the antibacterial activity of ornidazole.

In the liver, Wnt/β-catenin signaling is involved in regulating zonation and hepatocyte proliferation during homeostasis. We have examined Wnt gene expression and signaling after injury and we show by in situ hybridization that Wnts are activated by acute carbon tetrachloride (CCl4) toxicity. Following injury, peri-injury hepatocytes become Wnt-responsive, expressing the Wnt target gene Axin2. Lineage tracing of peri-injury Axin2+ hepatocytes shows that during recovery, the injured parenchyma becomes repopulated and repaired by Axin2+ descendants. Using single cell RNA sequencing (scRNA-seq), we show that endothelial cells are the major source of Wnts following acute CCl4 toxicity. Induced loss of β-catenin in peri-injury hepatocytes results in delayed repair and ultimately to injury-induced lethality, while loss of Wnt production from endothelial cells leads to a delay in the proliferative response after injury. Conclusion: Our Findings highlight the importance of the Wnt/β-catenin signaling pathway in restoring tissue integrity following acute liver toxicity and establishes a role of endothelial cells as an important Wnt-producing regulator of liver tissue repair following localized liver injury.

The binding properties between γ-lactone essences and HSA were investigated to explore interactional mechanism and influence of ligand side chains on binding via computer simulations, microscopy, and multiple-spectroscopies. Docking and molecular dynamics presented protein recognition mode with low fluctuations. NMR analysis revealed that the lactone ring of ligands was the main group bound to HSA. UV–vis and lifetime results revealed that the combination was static quenching mechanism with binding constants of 102–103 L/mol. FTIR and CD spectra showed conformational changes in the protein secondary structure induced by ligands. Side chains affect the binding process through steric hindrance and hydrophobicity. AFM images showed the four compounds caused different effects on molecular size of HSA. In conclusion, the binding ability and the protein secondary structure changes had a positive correlation with the length of side chain. These studies are beneficial for understanding the safety and biological action of γ-lactone essences.

Interaction between ulipristal acetate (UPA) and human serum albumin (HSA) was investigated in simulated physiological environment using multi-spectroscopic and computational methods. Fluorescence experiments showed that the quenching mechanism was static quenching, which was confirmed by the time-resolved fluorescence. Binding constants (

© 2015 Macmillan Publishers Limited. All rights reserved. The source of new hepatocytes in the uninjured liver has remained an open question. By lineage tracing using the Wnt-responsive gene Axin2 in mice, we identify a population of proliferating and self-renewing cells adjacent to the central vein in the liver lobule. These pericentral cells express the early liver progenitor marker Tbx3, are diploid, and thereby differ from mature hepatocytes, which are mostly polyploid. The descendants of pericentral cells differentiate into Tbx3-negative, polyploid hepatocytes, and can replace all hepatocytes along the liver lobule during homeostatic renewal. Adjacent central vein endothelial cells provide Wnt signals that maintain the pericentral cells, thereby constituting the niche. Thus, we identify a cell population in the liver that subserves homeostatic hepatocyte renewal, characterize its anatomical niche, and identify molecular signals that regulate its activity.

This study aims to investigate the interaction mechanism of a hypoglycemic agent, trelagliptin (TLP), and human serum albumin (HSA) through computer simulation and assisted spectroscopy methods. Computer simulation including molecular docking and molecular dynamics analysis was conducted under physiological conditions. Molecular docking results indicate that TLP bound to HSA at site I, and the binding behavior was mainly governed by hydrophobic force. Competitive experiments further verified the theoretical conclusion from molecular docking. Molecular dynamics simulation revealed that TLP indeed stably bound to site I of HSA in the hydrophobic subdomain IIA. Moreover, TLP presented a certain effect on the structural compactness of HSA. In molecular dynamics simulation, hydrogen bonds appeared, which suggested the reliability and stability of the combination. The binding energy of the stable phase is around −250 kJ/mol. Fluorescence quenching studies and time-resolved fluorescence analysis indicated that the evident fluorescence quenching phenomenon of HSA could be due to TLP binding initiated by static quenching mechanism. The binding constants (Ka) of the complex were found to be around 104 via fluorescence data, and the calculated thermodynamic parameters indicated that hydrophobic force played major role in the binding of TLP to HSA. Synchronous fluorescence and three-dimensional fluorescence results demonstrated that TLP slightly disturbed the microenvironment of amino residues. Circular dichroism spectra showed that TLP affected the secondary structure of HSA. The theoretical and experimental results showed excellent agreement.

Tertiary butylhydroquinone (TBHQ) is a water-insoluble antioxidant. In this study, three cyclodextrin inclusion complexes were prepared to improve the water solubility of TBHQ and expand its range of application. Analysis of phase solubility indicated that TBHQ can form 1:1 inclusion complex with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and dimethyl-beta-cyclodextrin (DM-β-CD) and 1:2 inclusion complex with beta-cyclodextrin (β-CD). The possible inclusion configuration between TBHQ and CDs was determined through FT-IR, PXRD, DSC, NMR, and SEM analyses. Results were validated by theoretical study of AutoDock molecular docking. The scavenging effects of the inclusion complexes were not effective on DPPH radical but higher on hydroxyl, superoxide and ABTS+ radicals than that of TBHQ monomer. Moreover, the water solubility of TBHQ increased after complexation with HP-β-CD and DM-β-CD. The stability of TBHQ is related to the type of storage materials used, and the stability can be improved by complexation with CDs.

Thiabendazole (TBZ), which is oxidized into 5-hydroxythiabendazole (5-OH-TBZ) in vivo, is a commonly used food preservative. Interactions of TBZ and 5-OH-TBZ with human serum albumin (HSA) were comprehensively studied via multiple spectroscopic methods and molecular docking. This study focussed on the mechanistic and structural information on binding of TBZ and 5-OH-TBZ to HSA to evaluate the impact of the food additive on HSA. 1H NMR spectra of the two ligands showed the binding exists. ITC and fluorescence spectroscopy results revealed that TBZ was a stronger ligand, with a binding constant of 105 l/mol and formed a more stable complex with HSA than did 5-OH-TBZ via electrostatic interaction. Spectroscopic results (UV–vis, FT-IR, and CD) showed that TBZ and 5-OH-TBZ caused conformational changes in HSA, in which α-helix and β-turn transformed into β-sheet, causing HSA structure to loosen. Docking programs showed that both TBZ and 5-OH-TBZ bound to HSA via IB.

Liposomes offer a method of delivering small molecules, nucleic acids, and proteins to sites within the body. Typically, bioactive materials are encapsulated within the liposomal aqueous core and liposomal phase transition is elicited by pH or temperature changes. We developed a new class of liposomes for the in vivo delivery of lipid-modified proteins. First, we show that the inclusion of a chromophore into the liposomal or vesosomal membrane renders these lipid vesicles extremely sensitive to very small (muJ) changes in energy. Next, we demonstrate that the lipid-modified Wnt protein is not encapsulated within a liposome but rather is tethered to the exoliposomal surface in an active configuration. When applied to intact skin, chromophore-modified liposomes do not penetrate past the corneal layer of the epidermis, but remain localized to the site of application. Injury to the epidermis allows rapid penetration of liposomes into the dermis, which suggests that mild forms of dermabrasion will greatly enhance transdermal delivery of liposome-packaged molecules. Finally, we demonstrate that topical application of Wnt3a liposomes rapidly stimulates proliferation of cells in the corneal layer, resulting in a thicker, more fibrillous epidermis.

Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context.