Cynaroside ameliorates methotrexate-induced enteritis in rats through inhibiting NLRP3 inflammasome activation.

Introduction: Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms. Methods: To assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation. Results: Administration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1ß in MTX-induced rats. Discussion: Collectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.

Effective photodegradation of rhodamine B and levofloxacin over CQDs modified BiOCl and BiOBr composite: Mechanism and toxicity assessment.

In this contribution, carbon quantum dots (CQDs) modified 3D-flower like BiOX (X = Cl, Br, I) photocatalyst were successfully prepared via a facile mechanical compounding method. The crystal structure, surface composition, morphologies, optical properties and photocatalytic activities were investigated in detail. The photocatalytic activity of the as-obtained photocatalyst were evaluated by degradation of rhodamine B (RhB) and Levofloxacin (LEV) under near IR-UV-vis light irradiation, the CQDs/BiOX composite displayed enhanced photocatalytic activity as compared with individual BiOX materials. The CQDs/BiOX composite had the outstanding light harvesting and electron transfer ability because of the ordered ultrathin nanosheet structure of the BiOX, the formation of metal Bi under photoinduction, and the synergistic effects between CQDs and pure BiOX. Antibacterial activity and effects on Rye seeds growth of the LEV degradation intermediate were also researched. Reactive-species-trapping experiments exhibited that h+ and O2- were the active reactive species during photodegradation process. This work provided an effective and simple strategy for designing QDs modified Bi-rich oxyhalides in organic pollutant containing wastewater treatment.

rGO/Bi2WO6 composite as a highly efficient and stable visible-light photocatalyst for norfloxacin degradation in aqueous environment.

Fabrication of binary composite has proved to be an efficient approach to improve the photocatalytic activity of monomer photocatalyst. In this contribution, an effective Reduced Graphene Oxide/Bismuth Tungsten Oxide (rGO/Bi2WO6) composite with outstanding photocatalytic activity was designed by employing Bi2WO6 as a primary photocatalyst and rGO as an electron acceptor and transporter for norfloxacin degradation in aquatic environment. The rGO/Bi2WO6 composite displayed higher photocatalytic activity compare with pure Bi2WO6, which could degrade about 87.49% of norfloxacin with 180 min under visible light irradiation. The results of the UV-vis diffuse reflection spectrum, photoluminescence spectra and transient photocurrent response implied that the enhanced photocatalytic activity of the rGO/Bi2WO6 composite could be attributed to the improved visible light-harvesting ability and the efficient charge separation ability. Additionally, the reactive-species-trapping experiments indicated that ⋅OH and e- played dominant roles during the photocatalytic degradation process. Four possible intermediates and two possible transformation pathways of norfloxacin degradation were detected by LC-MS. This present work provided a low-cost and facile green method to design of Bi-based composite.

Ursolic Acid Prevents Retinoic Acid-Induced Bone Loss in Rats.

OBJECTIVE: To examine the effects of ursolic acid (UA) on mitigating retinoic acid (RA)-induced osteoporosis in rats. METHODS: Fifty female Sprague-Dawley rats were randomly divided into the control group (n=10) and the osteoporosis group (n=40). The 40 osteoporosis rats were induced by 75 mg/(kg•d) RA once daily for 2 weeks, and then were randomly assigned to vehicle control (model), low-, middle-, and high-dose UA [(UA-L, UA-M, UA-H; 30, 60, 120 mg/(kg•d), respectively] groups (10 rats each). UA were administered once daily to the rats from the 3rd weeks for up to 4 weeks by gavage. Bone turnover markers [serum alkaline phosphatase (ALP), osteocalcin (OCN), urine deoxypyridinoline (DPD)] and other parameters, including serum calcium (S-Ca), serum phosphorus (S-P), urine calcium (U-Ca), urine phosphorus (U-P), and bone mineral density (BMD) of the femur, 4th lumbar vertebra and tibia, bone biomechanical properties and trabecular microarchitecture, were measured. RESULTS: The osteoporosis in rats was successfully induced by RA. Compared with the model group, UA-M and UA-H significantly reversed the RA-induced changes in S-P, U-Ca, U-P, ALP, OCN and urine DPD ratio and markedly enhanced the BMD of right femur, 4th lumbar vertebra and tibia (Plt;0.05 or Plt;0.01). Further, biomechanical test and microcomputed tomography evaluation also showed that UA-H drastically improved biomechanical properties and trabecular microarchitecture (Plt;0.05 or Plt;0.01). CONCLUSION: UA could promote bone formation, increase osteoblastic activity and reduce osteoclastic activity in rats, indicating that UA might be a potential therapeutic of RA-induced acute osteoporosis.

Design, synthesis, biological activities and DFT calculation of novel 1,2,4-triazole Schiff base derivatives.

Series of 1,2,4-triazole Schiff bases (2a-2d, 2f-2h and 3a-3h) have been designed and synthesized. The structure of title compounds was confirmed on the basis of their spectral data and elemental analysis. All the target compounds were screened for their in vitro antifungal activity and antibacterial activity. Two of the tested compounds (2a and 2b) exhibited significant antifungal activity against most fungi, especially compound 2a showed better antifungal activity than triadimefon. Meanwhile, the antibacterial activity assay also indicated compound 2a exhibited excellent antibacterial activities comparable to chloramphenicol. The SAR manifested no substitution at position 5 of the triazole ring caused an increase in activity, and 3-phenoxy phenyl group introduced in 1,2,4-triazole scaffold can enhance the antibacterial activity. The DFT calculation indicated triazole ring, S atom and benzene ring in both of the 2a and 3a make a major contribution to the activity.

Degradation and removal of Ceftriaxone sodium in aquatic environment with Bi2WO6/g-C3N4 photocatalyst.

Modern chemistry aims to identify outstanding photocatalytic materials for antibiotic degradation given the overuse and misuse of antibiotics. Herein, highly efficient heterojunction photocatalysts composed of Bi2WO6 nanoflowers (BW) and g-C3N4 nanosheets (CNNs) were successfully synthesized. The Bi2WO6/g-C3N4 (BW/CNNs) were presented for Ceftriaxone sodium degradation in the aquatic environment at low concentrations under visible light irradiation. The 40%-BW/CNNs showed excellent photocatalytic activity, and approximately 94.50% Ceftriaxone sodium was degraded under visible lightirradiation for 120 min. h+ and O2- played major roles compared with ·OH in the photocatalytic process. The degradation mechanism and the intermediate products were proposed to better understand the reaction process. Moreover, the as-prepared photocatalysts were highly stable in recycling photocatalytic experiments. Therefore, the photocatalysts prepared in the study showed outstanding photocatalytic activity and potential applications in inhibiting environmental pollution. In addition, this work provides a new insight for constructing other high-performance, low-cost photocatalysts for wastewater treatment.

A targeted drug delivery system based on folic acid-functionalized upconversion luminescent nanoparticles.

In this paper, multifunctional upconversion luminescent NaYF4:Yb,Er nanoparticles with excellent hollow mesoporous structure were first fabricated. The effects of various reaction conditions on the morphology and size of the as-prepared samples were investigated in detail and Ostwald ripening effect was adapted to explain the formation mechanism of the HMUCNPs. Then, folic acid, a well-known ligand for the selective targeting of drugs into tumor cells, was conjugated to the surface of the hollow mesoporous structured upconversion luminescent nanoparticles (HMUCNPs) via amide reaction for targeted delivery of anticancer drugs so as to enhance the therapeutic efficacy. The properties were extensively studied, which indicated the obtained samples showed a typical hollow mesoporous structure and excellent upconversion luminescence that were useful for cell imaging and drug delivery. Drug storage/release properties were demonstrated to be pH responsive, in which the drug release might be beneficial at the reduced pH in certain cancerous tissues for targeted release and controlled therapy at the pathological sites. Meanwhile, DOX-NaYF4:Yb,Er-FA HMUCNPs exhibited greater cytotoxicity than free doxorubicin hydrochloride because folic acid-conjugated HMUCNPs can be specifically taken up by FR-positive KB cells via a receptor-mediated endocytosis. Therefore, the folic acid-functionalized nanoparticles combining upconversion luminescent property and hollow mesoporous structure have potential for simultaneous targeted anticancer drug delivery and cell imaging.

Incorporation of lanthanide (Eu(3+)) ions in ZnS semiconductor quantum dots with a trapped-dopant model and their photoluminescence spectroscopy study.

Doping quantum dots (QDs) with lanthanide (Ln) ions is promising to modify the optical properties of QDs, but incorporating Ln(3+) ions into QD hosts remains a challenge. In this work, we adopt the trapped-dopant model for fabricating Eu-doped ZnS QDs via direct wet chemical synthesis. Sharp Eu dopant photoluminescence (PL) was observed in the PL spectra of the as-prepared Eu-doped ZnS QDs and the bands at ~590, ~618 and ~695 nm were assigned to transitions from (5)D0 to (7)F1, (7)F2 and (7)F4, respectively. Quenching of the ZnS bandgap PL and enhancement of the Eu dopant PL were observed with increasing Eu(3+) doping concentration, and also, the excitation spectra for Eu emission (618 nm) were similar to the typical excitonic features of the ZnS host. These spectroscopic results, as well as the XRD and EDS data, demonstrated that Eu(3+) ions were incorporated in the ZnS host rather than just on the surface, and the Eu dopant PL was derived from energy transfer from the QD host to Eu(3+) rather than direct excitation of Eu(3+). By surface passivation, the sharp Eu emission was well-separated from the ZnS bandgap emission, which led to a good signal-to-noise ratio for more sensitive detection.

Aggregation-induced emission of 1,8-naphthalimide-casein micelle: investigation by synchronous spectrographic method.

A novel 1,8-naphthalimide probe 1, bearing two acetic-acid moieties was synthesized. The acetic-acid groups, docked into the sub-domains of casein micelle and bound with tryptophan residues, and the 1,8-naphthalimide chromophore adsorbed on the surface of casein micelle, forming a supermolecule, 1-casein micelle, which exhibited the aggregation-induced synchronous emission (AISE) characters. The effect of pH on the intensity of supermolecule was investigated, and the result indicated that the emission enhancement was mainly due to the 1,8-naphthalimide chromophore aggregated onto the casein micelle. Based on AISE, a novel casein quantification method was developed, which exhibited a good linear range of 0.05-10.0 µg ml(-1) and 0.07-9.5 µg ml(-1) with the detection limits of 2.8 and 3.0 ng ml(-1) . The effects of metal ions and pH on the system of 1-casein micelle were investigated. The proposed method was applied to determine casein in milk samples, and the results were in good agreement with the result of the Biuret method.

Enhanced distribution and anti-tumor activity of ergosta-4,6,8(14),22-tetraen-3-one by polyethylene glycol liposomalization.

Ergosta-4,6,8(14),22-tetraen-3-one (ergone) was isolated from P. umbellatus, which has been demonstrated to possess a variety of pharmacological activities in vivo and in vitro. The purpose of this study was to evaluate the potent ergone formulations for cancer chemotherapy, the liposomal formulations were less toxic and provide longer systemic circulation time were selected as candidates of nanocarriers for ergone. The effect of modification polyethylene glycol (PEG) on the pharmacokinetics of liposome showed that the retaining time of ergone in blood circulation was prolonged by modified PEG. Moreover, the results of pharmacokinetic analysis showed that of PEG liposome was about 2.8 times higher than that of free PEG liposome after intravenous injection into normal rats due to the lower distribution into the reticuloendothelial system tissues. Since PEG liposome was able to stably encapsulate ergone in blood, area under plasma concentration-time curve of ergone was also extensively enhanced after intravenous dosing of ergone-PEG liposome into normal rats. In the in vivo studies utilizing solid tumor-bearing mice, it was confirmed that ergone-PEG liposome delivered remarkably larger amount of ergone to tumor tissue and provided more significant anti-tumor activity than free ergone. In conclusion, PEG liposome was an effective delivery formulation to achieve increased ergone release in tumor and therapeutic efficacy.

Study on photophysical and aggregation induced emission recognition of 1,8-naphthalimide probe for casein by spectroscopic method.

A novel water-soluble 1,8-naphthalimide derivative 1, bearing two acetic carboxylic groups, exhibited fluorescent turn-on recognition for casein based on the aggregation induced emission (AIE) character. The photophysical properties of 1 consisting of donor and acceptor units were investigated in different solutions. The fluorescence intensity decreased through taking advantage of twisted intramolecular charge transfer (TICT) and self-association emission with increasing solvent polarity. Moreover, the spectral red-shift and intensity quench in protic solvents were caused by the excited-state hydrogen bond strengthening effect. Density Functional Theory (DFT) calculations revealed that 1 exhibited a strong TICT character. The AIE mechanism of 1 with casein was due to 1 docked in the hydrophobic cavity between sub-micelles and bound with Tyr and Trp residues, resulting in the aggregation of 1 on the casein surface and emission enhancement. Based on this, a novel casein assay method was developed. The proposed exhibited a good linear range from 0.1 to 22 µg mL(-1), with the detection limit of 2.8 ng mL(-1). Satisfactory reproducibility, reversibility and a short response time were realized. This method was applied to the determination of casein in milk powder samples and the results were in good agreement with the result of Biuret method.

A sensitive spectrofluorometric method for determination of ergosta-4,6,8(14),22-tetraen-3-one in rat plasma, feces, and urine for application to pharmacokinetic studies using cerium(III) as a probe.

Ergosta-4,6,8(14),22-tetraen-3-one (ergone) isolated from Polyporus umbellatus possesses a variety of pharmacological activities in vivo and in vitro, including cytotoxic, diuretic, and immunosuppressive effect. The interaction of cerium ions (Ce(3+)) with ergone was studied by fluorescence and absorption spectroscopy. Spectra data revealed that Ce(3+) ions exhibited emission maxima around 350 nm when the excitation wavelength was fixed at 255 or 290 nm, and the fluorescence of Ce(3+) ions was quenched by the addition of ergone, indicating that a Ce(3+)-ergone complex was formed. According to the modified Benesi-Hildebrand equation, the binding constant of interaction of Ce(3+) ions with ergone was obtained at room temperature. Based on this, a sensitive spectrofluorometric method using Ce(3+) ions as a probe was applied for the identification and quantification of ergone in rat plasma, feces, and urine. The linear ranges of the calibration curves were 1.31 to 4.50 µM for plasma, 1.12-9.87 µM for feces, and 1.28-3.42 µM for urine, and the ergone recoveries were found to be 97.1 ± 0.9%, 98.2 ± 0.7% and 96.5 ± 1.4% for plasma, feces, and urine, respectively. The intraday and inter-day relative standard deviations were less than 9.7%. The proposed spectrofluorometric method is simple and rapid for the quantitative determination of ergone in rat plasma, feces, and urine, and it is affordable for most laboratories because it has few requirements and uses low cost, easy to operate equipment.

Folate-functionalized nanoparticles for controlled ergosta-4,6,8(14),22-tetraen-3-one delivery.

To improve the therapeutic effect of ergosta-4,6,8(14),22-tetraen-3-one (ergone), a folate-decorated ergone-bovine serum albumin nanoparticles (abbreviated FA-ergone-BSANPs) was prepared. The properties were extensively studied by Zetasizer Nano Particle Size Analyzer and TEM, which indicated the prepared nanoparticles were spherical in shape and uniform in size with a zeta potential of -23.8 mV. The drug-loading capacity also has been determined with drug loading content of 2.73% and encapsulation efficiency of 61.8%. In vitro release studies proved the much slow drug release from the nanoparticles during circulating in the blood stream and the increase of drug release at the target sites. The FA-ergone-BSANPs showed enhanced cellular uptake, increased targeting capacity, and increased cytotoxicity against KB cells over-expressing folate receptor (FR), which indicated that its potent cell-killing activity is specific for cells that express the FR. In vivo experiment also confirmed that FA-ergone-BSANPs represent a FR-targeted chemotherapeutic that can produce potent activity against FR-positive tumors. In conclusion, this report has a great significance in pharmacology and clinical medicine as well as methodology. Further detailed dose-optimization studies will be required for better understanding in vivo pharmacokinetic and bio-distribution behaviors.

Solvent effects on the absorption and fluorescence spectra of rhaponticin: experimental and theoretical studies.

Rhaponticin (RH) possesses a variety of pharmacological activities including potent antitumor, antitumor-promoting, antithrombotic, antioxidant and vasorelaxant effects. The fundamental photophysics of RH is not well understood. In this work, solvent effect on the photoluminescence behavior of RH was studied by fluorescence and absorption spectra. The bathchromic shift was observed in absorption and fluorescence spectra with the increase of solvents polarity, which implied that transition involved was π→π. A quantitative estimation of the contribution from different solvatochromic parameters, like normalized transition energy value (E(T)(N)), was made using the linear stokes shift (Δν) relationship based on the Lippert-Suppan equation. The ground state and excited state dipole moments were calculated by quantum-mechanical second-order perturbation method as a function of the dielectric constant (ε) and refractive index (n). The result was found to be 2.23 and 3.67D in ground state and excited state respectively. The density functional theory (DFT) was used to obtain the most stable structure, electronic excitation energy, dipole moments and charge distribution. The analysis revealed that the RH exhibited strong photoinduced intramolecular charge transfer (ICT), and the intermolecular hydrogen bonding ability of the solvent was the most important parameter to characterize the photophysics behavior of RH. The hydrogen bonding effect occurred at the localized electron-acceptor oxygen at the glycoside bond. The experimental and theoretical results would help us better understand the photophysical properties of RH.

Synthesis and biological evaluation of a folate-targeted rhaponticin conjugate.

To improve the therapeutic effect of rhaponticin (RHA), a folate receptor (FR) targeted RHA conjugate was synthesized by utilizing a hydrophilic peptide spacer linked to folic acid (FA) via a releasable disulfide linker. This water-soluble conjugate was found to retain high affinity for FR-positive cells, and it produced specific, dose-responsive activity in vitro. Treatment of FRHA with a reducing agent indicated that the amino-reactive derivative of RHA would be released spontaneously following disulfide bond reduction within the endosomes. FRHA also proved to be active predominantly specific against FR-positive syngeneic and xenograft models in vivo, and possible curative activity resulted with minimal to moderate toxicity. The FRHA conjugate greatly enhanced the therapeutic effects and reduced the toxicity of RHA. In conclusion, FRHA represents a folate-targeted chemotherapeutic that can produce potent activity against established sc tumors. Hence, this report has a great significance in pharmacology and clinical medicine as well as methodology.

Fluorescent turn-on detection and assay of water based on 4-(2-dimethylaminoethyloxy)-N-octadecyl-1,8-naphthalimide with aggregation-induced emission enhancement.

The photophysical properties of 4-(2-dimethylaminoethyloxy)-N-octadecyl-1,8-naphthalimide (DON) consisting of donor and acceptor units were investigated in different solutions. Changing from a non-polar to a polar solvent increased the solvent interaction and both the excitation and emission spectra were shifted to longer wavelength and intensity decreased through taking advantage of twisted intramolecular charge transfer (TICT). Density functional theory (DFT) calculations and spectral analyses revealed that such fluorophores were capable of sensing protons by intramolecular charge transfer (ICT). Empirical and quantum mechanical calculations showed that the electron donating effect of the dimethylamino group decreased the change in dipole moment on excitation which resulted in a fluorescence quantum yield remarkably enhanced as the solvent polarity increased. In alkaline media the fluorescence of DON was quenched owing to photoinduced electron transfer being disabled in acidic media. The pK(a) of the 1,8-naphthailimide dye was 6.70, which defines the dye as a highly efficient "off-on" switch. DON exhibited a typical aggregation-induced emission enhancement (AIEE) behavior that it is virtually nonemissive in organic solvent but highly luminescent in water, as a result of the restriction of free intramolecular rotation of a C-N bond and the non-planar configuration in the aggregate state. The hydrophobicity of octadecyl group provided DON with a fluorescent response to water based on AIEE and the water-dependent spectral characteristics of DON, and the AIEE of DON caused by the effect of water and formation of J-aggregation states. In the range of 0-79.8% (v/v), the fluorescence intensity of DON in acetone solution increased as a linear function of the water content. The optimum detection limits were of 0.011%, 0.0021%, and 0.0033% of water in acetone, ethanol, and acetonitrile, respectively. Satisfactory reproducibility, reversibility and a short response time were realized.

Synthesis and characterization of TiO(2) nanoparticles: applications in research on the interaction of colloidal TiO(2) with human serum albumin by fluorescence spectroscopy.

Titanium dioxide (TiO(2)) nanoparticles (NPs) are widely used as an important kind of biomaterials due to their large surface area, enhanced chemical reactivity and easy penetration into cells. Nano TiO(2) with pure anatase phase was successfully prepared by solvothermal method. Its particle size was about 21 nm, while the larger specific surface area of TiO(2) was 77.43 m(2)/g. The interaction of colloidal TiO(2) with human serum albumin was studied by using absorption spectra and fluorescence spectra. The apparent binding constants (K) were 345.780 × 10(5), 4.376 × 10(5), 0.035 × 10(5) at 298, 303 and 308 K, respectively. In addition, the number of binding sites (n) was gradually decreased with the increase of temperature, which indicated that the quenching mechanism of albumin by colloidal TiO(2) was static fluorescence quenching process. Based on fluorescence resonance energy transfer, the energy transfer efficiency (E) and critical transfer distance (r(0)) between donor (human serum albumin, HSA) and acceptor (colloidal TiO(2)) were calculated to be 0.862 and 6.244 nm, which suggested that non-radiative energy transfer occurred between TiO(2) and HSA. Furthermore, the conformational changes of HSA were shown by synchronous fluorescence.