ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown. AIM OF THE STUDY: To clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms. MATERIALS AND METHODS: We used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined. RESULTS: FTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80+ macrophage cell infiltration and Ly-6G+ neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ. CONCLUSION: FTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ.
Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Drugs, Chinese Herbal , Animals , Cholesterol, LDL , Collagen , Diabetes Mellitus/drug therapy , Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Female , Humans , Inflammation/drug therapy , Interleukin-17 , Kidney , Male , Medicine, Chinese Traditional , Mice , NF-kappa B , Proteinuria/drug therapyABSTRACT
This study aimed to evaluate the effects of the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) on cartilage injury in an osteoarthritis (OA) rat model. Sodium iodoacetate (3 mg/50 µL) was used to induce OA in the left knee joint of rats. On day 14 after OA induction, 50 µL of SVF (5 × 106cells), ADSCs (1 × 106 cells), or 0.9% normal saline (NS) was injected into the left knee-joint cavity of each group. The macroscopic view and histological sections revealed that the articular cartilage in the NS group was damaged, inflamed, uneven and thin, and had hyperchromatic cell infiltration. Notably, the cartilage surface had recovered to nearly normal and appeared smooth and bright on day 14 in the SVF and ADSC groups. Additionally, the white blood cell counts in the SVF and ADSC groups were higher than those in the NS group on day 14. Plasma IL-1ß levels on days 7 and 14 were reduced in the SVF and ADSC groups. These results indicated that both SVF and ADSC treatments may assist in articular cartilage regeneration after cartilage injury. Cell therapy may benefit patients with OA. However, clinical trials with humans are required before the application of SVF and ADSC treatments in patients with OA.
Subject(s)
Cartilage, Articular/growth & development , Cell- and Tissue-Based Therapy , Osteoarthritis/therapy , Stromal Vascular Fraction/transplantation , Adipocytes/transplantation , Animals , Cartilage, Articular/pathology , Disease Models, Animal , Humans , Mesenchymal Stem Cells , Osteoarthritis/pathology , Rats , Regeneration/geneticsABSTRACT
This letter reports on a novel cost-efficient and multifunctional barcode-like sensors array (BLSA) printed with a conductive bioinspired smart ink. The conductive ink (P@G ink), which can be further chemically engineered with different organic ligands, was generated via facile one-pot hydrothermal reduction of graphene oxide (GO) in dopamine (DA) as coreductan Usingvarious chemical derivatives of the P@G inks on a flexible substrate (e.g., Kapton), a highly integrated BLSA as well as smart nose/tongue mimic array were generated for simultaneous sensing and distinguishing of complex physical and chemical stimuli, including temperature, light, air pressure, relative humidity, and volatile organic compounds (VOCs). Due to these very attractive features, the reported P@G ink-based BLSA would have the potential for unique opportunities regarding "all-in-one"-yet cost-effective-disposable electronics and sensors.
Subject(s)
Electrical Equipment and Supplies , Ink , Air Pressure , Biomimetics , Dopamine , Graphite , Humidity , Light , Temperature , Volatile Organic CompoundsABSTRACT
A protein/lanthanide complex (BSA/Tb3+)-based sensor array in two different pH buffers has been designed for high-throughput recognition and time-resolved fluorescence (TRF) detection of metal ions in biofluids. BSA, which acted as an antenna ligand, can sensitize the fluorescence of Tb3+ (i.e., antenna effect), while the presence of metal ions would lead to the corresponding conformational change of BSA for altering the antenna effect accompanied by a substantial TRF performance of Tb3+. This principle has also been fully proved by both experimental characterizations and coarse-grained molecular dynamics (CG-MD) studies. By using Tris-HCl buffer with different pHs (at 7.4 and 8.5), 17 metal ions have been well-distinguished by using our proposed BSA/Tb3+ sensor array. Moreover, the sensor array has the potential to discriminate different concentrations of the same metal ions and a mixture of metal ions. Remarkably, the detection of metal ions in biofluids can be realized by utilizing the presented sensor array, verifying its practical applications. The platform avoids the synthesis of multiplex sensing receptors, providing a new method for the construction of convenient and feasible lanthanide complex-based TRF sensing arrays.
Subject(s)
Body Fluids/chemistry , High-Throughput Screening Assays , Metals, Heavy/analysis , Serum Albumin, Bovine/chemistry , Animals , Cattle , Fluorescence , Hydrogen-Ion Concentration , Molecular Dynamics Simulation , Spectrometry, Fluorescence , Time FactorsABSTRACT
Recent years have witnessed thriving progress of flexible and portable electronics, with very high demand for cost-effective and tailor-made multifunctional devices. Here, we report on an ingenious origami hierarchical sensor array (OHSA) written with a conductive ink. Thanks to origami as a controllable hierarchical framework for loading ink material, we have demonstrated that OHSA possesses unique time-space-resolved, high-discriminative pattern recognition (TSR-HDPR) features, qualifying it as a smart sensing device for simultaneous sensing and distinguishing of complex physical and chemical stimuli, including temperature, relative humidity, light and volatile organic compounds (VOCs). Of special importance, OSHA has shown very high sensitivity in differentiating between structural isomers and chiral enantiomers of VOCs - opening a door for wide variety of unique opportunities in several length scales.
ABSTRACT
In this work, we present a novel facile strategy for green synthesis of polyethyleneimine (PEI)-capped carbon dots (PEI-CDs), in which citric acid and PEI were chosen as reactants and highly fluorescent PEI-CDs could be readily obtained via a simple one-pot refluxing under 120 °C within 2 H. Fluorescence studies indicate that the as-prepared PEI-CDs exhibit strong fluorescence emission at 446 nm with excitation at 365 nm. Upon the sequential addition of Cu2+ and H2 S, PEI-CDs result in an interesting "ON-OFF-ON" three-state emission responses, promising a bifunctional sensory platform. Moreover, the Cu2+ /H2 S-facilated reversible fluorescence changes of PEI-CDs have demonstrated the design of an INHIBIT logic system based on Boolean logic.
Subject(s)
Carbon/chemistry , Copper/analysis , Fluorescent Dyes/chemistry , Hydrogen Sulfide/analysis , Logic , Polyethyleneimine/chemistry , Quantum Dots/chemistry , Biological Assay/methods , Optical Imaging , Spectrometry, FluorescenceABSTRACT
Tb3+-doped carbon dots (Tb3+@CDs) were prepared in a facile hydrothermal method by using ammonium citrate as carbon source and Tb3+ as dopant. A 15-bp GT-rich single-strand DNA (ssDNA) was introduced to sensitize Tb3+ via the antenna effect for generating two fluorescence signals (CDs and Tb3+), forming a conjugate of Tb3+@CDs/ssDNA. The ratiometric fluorescence of Tb3+@CDs/ssDNA could be reversibly regulated by Ag+ and Cys, in which the fluorescence peak at 546â¯nm of Tb3+ could be switched to "On" or "Off" as the signal indicator while the fluorescence peak at 444â¯nm of CDs remained constant as the build-in reference. The proposed Ag+/Cys-mediated reversible fluorescence changes in Tb3+@CDs/ssDNA was also proven for the design of a self-calibrating ratiometric fluorescence logic system. By integrated with the specific reaction between H2O2 and Cys, Tb3+@CDs/ssDNA was applied for ratiometric fluorescence detection of H2O2. More importantly, the sensing strategy could be further successfully extended to the monitoring of H2O2-produced oxidase-related reactions, such as GOx-biocatalyzed oxidation of glucose (the limit of detection: 0.06⯵M) and was well applied in rat serum compared to commercial kits. This work unveiled a novel ratiometric fluorescent design, which is cost-effective, simple to prepare and easy-to-use without chemical modification or fluorescence labeling.
Subject(s)
Biosensing Techniques/methods , Carbon/chemistry , DNA, Single-Stranded/chemistry , Nanoparticles/chemistry , Oxidoreductases/metabolism , Terbium/chemistry , Animals , Base Sequence , Biocatalysis , Blood Glucose/analysis , Calibration , Cysteine/chemistry , Cystine/chemistry , DNA, Single-Stranded/genetics , Hydrogen Peroxide/chemistry , Male , Models, Molecular , Molecular Conformation , RatsABSTRACT
Screening functional DNA that can fruitfully interact with metal ions is a long-standing hot topic in the fields of biotechnology, medicine, and DNA-based sensors. In this paper, we focus on the chemistry of europium(III) (Eu) coupled with single-stranded DNA (ssDNA), and we innovatively unveil that cytosine- and thymine-rich ssDNA oligomers (e.g., C16 and T16) can be effective antenna ligands to sensitize the luminescence of Eu. Luminescence lifetime spectroscopy, circular dichroic (CD) spectroscopy, and isothermal titration calorimetry (ITC) have been used to systematically characterize the interaction involved between Eu and ssDNA. In light of the resultant sequence-dependent performances, the long luminescence lifetime Eu/ssDNA-based label-free and versatile probes are further devised as a pattern distinction system for time-resolved luminescent (TRL) sensing applications. The interactions of metal ions and ssDNA can distinctively shift the antenna effect of ssDNA toward Eu as accessible pattern signals. As a result, as few as two Eu/ssDNA label-free TRL probes can discriminate 17 metal ions via principal component analysis (PCA). In addition, thiols can readily capture metal ions to switch the luminescence of Eu/ssDNA probes initially altered by metal ions. Hence, four Eu/ssDNA-metal ion ensembles are demonstrated to be a powerful label-free TRL sensor array for pattern differentiation of eight thiols and even chiral recognition of cysteine enantiomers with different concentrations. Moreover, the sensitive TRL detection of thiols in biofluids can be successfully realized by using our method, promising its potential practical usage. This is the first report of a ssDNA-sensitized Eu-based TRL platform for label-free yet multifunctional background-free sensing and would open a door for sprouting of more novel lanthanide ion/DNA-relevant strategies toward widespread applications.
Subject(s)
DNA/chemistry , Europium/chemistry , DNA Probes/chemistry , DNA, Single-Stranded/chemistry , LuminescenceABSTRACT
Dual-mode optical assays are becoming more popular and attractive because they would provide robust detailed information in biochemical analysis. We herein unveil a novel dual-mode optical (i.e., UV-vis absorption and fluorescence) method for multifunctional sensing of phosphate compounds (PCs) (e.g., nucleotides and pyrophosphate) based on pattern recognition, which innovatively employs only one kind of porphyrin/lanthanide-doped upconversion nanoparticles (Ln-UCNPs) hybrid integrated with a facile pH-regulated strategy as the sensor array. An easy-to-obtain porphyrin hydrate (tetraphenylporphyrin tetrasulfonic acid hydrate, TPPS) can assemble onto the ligand-free Ln-UCNPs to construct the organic/inorganic hybrid (TPPS/Ln-UCNPs), leading to a new absorption band to quench the upconversion fluorescence of Ln-UCNPs due to fluorescence resonance energy transfer (FRET). The dual-mode optical performances of TPPS/Ln-UCNPs are characteristically correlated with the pH in aqueous solution. Thus, as a proof-of-concept design, three types of TPPS/Ln-UCNPs (TPPS/Ln-UCNPs4, TPPS/Ln-UCNPs4.5, and TPPS/Ln-UCNPs5) were prepared by using buffers with different pH (at 4, 4.5, and 5) to form our proposed sensor array, which would result in individual dual-mode optical response patterns upon being challenged with PCs for their pattern recognition through a competitive mechanism between TPPS and PCs. The results show that three TPPS/Ln-UCNPs n sensors can successfully permit the sensitive detection of 14 PCs and differentiate them between different concentrations, as well as a mixture of them. The pH-dependent TPPS/Ln-UCNPs promises the simple, yet powerful discrimination of PCs via pattern recognition, would prospectively stimulate and expand the use of organic/inorganic hybrid toward more biosensing applications.
Subject(s)
Biosensing Techniques , Chemistry Techniques, Analytical , Inorganic Chemicals/analysis , Organic Chemicals/analysis , Hydrogen-Ion Concentration , Principal Component AnalysisABSTRACT
There is a close correlation between body health and the level of biofluid-derived metal ions, which makes it an attractive model analyte for noninvasive health monitoring. The present work has developed a novel nose/tongue-mimic chemosensor array based on bioinspired polydopamine/polyethylenimine copolymers (PDA/PEI n) for label-free fluorescent determination of metal ions in biofluids. Three types of PDA/PEI n (PDA/PEI6, PDA/PEI18, and PDA/PEI48) were prepared by using different concentrations of PEI to construct the proposed sensor array, which would lead to unique fluorescence response patterns upon challenged with metal ions for their pattern discrimination. The results show that as few as 3 PDA/PEI n sensors can successfully realize the largescale sensitive detection of metal ions in biofluids. Moreover, we have demonstrated that PDA/PEI n sensors are qualified for lifetime-based pattern discrimination application. Furthermore, the sensors can distinguish between different concentrations of metal ions, as well as a mixture of different metal ions in biofluids, even the mixtures with different valence states. The method promises the simple, rapid, sensitive, and powerful discrimination of metal ions in accessible biofluids, showing the potential applications in the diagnosis of metal ion-involved diseases.
Subject(s)
Biomimetic Materials/chemistry , Clinical Chemistry Tests/instrumentation , Indoles/chemistry , Metals/analysis , Nose , Polyethyleneimine/chemistry , Polymers/chemistry , Tongue , HumansABSTRACT
Recent years have witnessed the rapid development of pattern-based sensors due to their potential to detect and differentiate a wealth of analytes with only few probes. However, no one has found or used the combination of DNA and terbium(III) (Tb) as a pattern recognition system for large-scale mix-and-measure assays. Here we report for the first time that DNA-sensitized Tb (DNA/Tb), as a label-free and versatile "chemical nose/tongue", can be employed for wide-scale time-gated luminescent (TGL) monitoring of metal ions covering nearly the entire periodic table in a cost-effective fashion. A series of guanine/thymine (G/T)-rich DNA ligands was screened to sensitize the luminescence of Tb (referring to the antenna effect) as smart pattern responders to metal ions in solution, and metal ion-DNA interactions can differentially alter the antenna effect of DNA toward Tb as pattern signals. Our results show that as few as 3 DNA/Tb label-free sensors could successfully discriminate 49 analytes, including alkali-metal ions, alkaline-earth-metal ions, transition/post-transition metal ions, and lanthanide ions. A blind test with 49 metals further confirmed the discriminating power of DNA/Tb sensors. Moreover, the lifetime-based pattern recognition application using DNA/Tb sensors was also demonstrated. This DNA/Tb pattern recognition strategy could be extended to construct a series of "chemical noses/tongues" for monitoring various biochemical species by using different responsive DNA ligands, thus promising a versatile and powerful tool for a sensing application and investigation of DNA-involving molecular interactions.
Subject(s)
Biosensing Techniques/methods , DNA/chemistry , Luminescent Agents/chemistry , Luminescent Measurements/methods , Metals/analysis , Terbium/chemistry , Environmental Monitoring/methods , Guanine/chemistry , Ligands , Luminescence , Thymine/chemistry , Water Pollutants, Chemical/analysisABSTRACT
Thiols play a crucial role in various biological processes, and the discrimination of thiols in biofluids is a significant but difficult issue. Herein, a facile label-free non-invasive fluorescent sensor array has been presented based on PDA/PEIn-Cu2+ in three different pH buffer solutions for pattern discrimination of thiols and chiral recognition of cysteine (Cys) enantiomers in biofluids toward health monitoring. The proposed sensor array was fabricated based on the fact that Cu2+ has a strong affinity toward thiols, which prevents Cu2+ from binding PDA/PEIn, and the fluorescence properties of PDA/PEIn were recovered to a certain degree. Different thiols exhibited different affinities toward Cu2+, generating distinct fluorescence response patterns. These response patterns are characteristic for each thiol and can be discriminated by principal component analysis (PCA). In this work, three types of PDA/PEI48-Cu2+ sensors (PDA/PEI48-Cu4 2+, PDA/PEI48-Cu4.5 2+ and PDA/PEI48-Cu5 2+) were prepared by using acetate buffer with different pHs (at 4, 4.5, and 5) to form our proposed sensor array, which could realize the pattern discrimination of 8 thiols. Moreover, we successfully realized the sensitivity and selectivity assays to these thiols. Furthermore, the proposed sensor array could discriminate mixtures of thiols as well as the chiral recognition of mixtures of Cys enantiomers, promising its potential practical usage. Significantly, the resultant practical application in real samples showed that it could be a fascinating assay for the development of non-invasive diagnosis. This method promises the facile, sensitive and powerful discrimination of thiols in biofluids and would sprout more relevant strategies toward a broad range of applications.
ABSTRACT
The authors made a theoretical analysis and experiment research on the relation of time-resolved coherent anti-Stokes Raman scattering (T-CARS) intensity and the sample concentrations in this paper. It was proved experimentally that the T-CARS intensity is quadratic at the concentration higher than 35%, but is linear with the sample concentration at the concentration lower than 20%, which fits with theoretical analysis. And the research results correct inaccurate previous perceptions, which is conducive to better interpretation and application of the CARS process. The linear relation between the intensity of the CARS with the sample concentration at low concentrations indicates that the CARS is allowed for direct and precise concentration measurements, therefore it will be of great importance in biology and biochemistry.
Subject(s)
Spectrum Analysis, Raman/methods , Biochemistry/methods , Biology/methods , Models, TheoreticalABSTRACT
In the present paper, the authors used the time-resolved coherent anti-Stokes Raman scattering (CARS) spectroscopy based on supercontinuum developed by ourselves to acquire simultaneously the molecular vibration spectrum and vibrational dephasing time of the molecular various vibrational modes. Using benzonitrile as the sample, the authors measured its vibrational relaxation processes at its five typical vibrational modes and obtained their vibrational dephasing time respectively. In the experiment, the authors also found the phenomenon that oscillations appear in the vibrational dephasing of plane bending vibration mode of benzene ring in benzonitrile, which was caused by superposition of the two adjacent normal vibrational modes excited simultaneously. After mixing benzonitrile with anhydrous ethanol, the authors also measured their vibrational dephasing time. This method is capable of monitoring the changes of the molecular characteristics and its micro-environment, therefore it will find widespread applications in biology, chemistry and materials science.