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1.
Appl Microbiol Biotechnol ; 106(2): 799-810, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34939134

ABSTRACT

African swine fever (ASF) is an acute and highly contagious infectious disease caused by the African swine fever virus (ASFV). Currently, there is no vaccine against ASF worldwide, and no effective treatment measures are available. For this reason, developing a simple, rapid, specific, and sensitive serological detection method for ASFV antibodies is crucial for the prevention and control of ASF. In this study, a 1:1 mixture of gold-labeled p30 and p72 probes was used as the gold-labeled antigen. The p30 and p72 proteins and their monoclonal antibodies were coated on a nitrocellulose membrane (NC) as a test (T) line and control (C) line, respectively. A colloidal-gold dual immunochromatography strip (ICS) for ASFV p30 and p72 protein antibodies was established. The results showed that the colloidal-gold dual ICS could specifically detect ASFV antibodies within 5-10 min. There was no cross-reaction after testing healthy pig serum; porcine reproductive and respiratory syndrome virus (PRRSV), foot-and-mouth disease type A virus (FMDV-A), foot-and-mouth disease type O virus (FMDV-O), porcine circovirus type 2 (PCV-2), and classical swine fever virus (CSFV) positive sera. A positive result was obtained only for the positive control P1. The sensitivity of the test strips was 1:256, which was equivalent to that of commercially ELISA kits. Their coincidence rate with the two commercial ASFV ELISA antibodies detection kits was higher than 98%. The test strips were stably stored at 18-25 °C and 4 °C for 4 and 6 months, respectively. The colloidal-gold dual ICS prepared in this study had high sensitivity and specificity and were characterized by rapid detection, simple operation, and easy interpretation of results. Therefore, they are of great significance to diagnose, prevent, and control African swine fever. KEY POINTS: • We establish an antibody detection that is quick and can monitor an ASF infection. • We observe changes in two protein antibodies to dynamically monitor ASF infection. • We use diversified detection on a single test strip to detect both antibodies.


Subject(s)
African Swine Fever Virus , African Swine Fever , African Swine Fever/diagnosis , Animals , Chromatography, Affinity , Enzyme-Linked Immunosorbent Assay , Gold Colloid , Swine
2.
Nano Lett ; 21(10): 4484-4493, 2021 05 26.
Article in English | MEDLINE | ID: mdl-33978427

ABSTRACT

Acute pneumonia can greatly increase the vulnerable risk of atherosclerotic plaque and contribute to the mortality of cardiovascular disease. To accurately assess the rupture risk caused by acute pneumonia, we developed a novel kind of ratiometric semiconducting polymer nanoparticle (RSPN) for photoacoustic imaging of vulnerable plaque in apolipoprotein E-deficient mice complicated with pneumonia. Specifically, RSPN can react with O2•- and exhibit the enhanced photoacoustic signals at about 690 nm, while 800 nm is regarded as an internal photoacoustic reference. As a result, RSPN can provide reliable determination of O2•- within aortic atherosclerosis by analyzing the ratios of photoacoustic signals, which can successfully reflect the oxidative stress level in vulnerable plaque. Therefore, RSPN enable to specifically distinguish plaque-bearing mice and plaque-bearing mice complicated with pneumonia from healthy mice, which provides a promising tool to predict the vulnerability of plaque for reducing the mortality of atherosclerotic-induced cardiovascular disease.


Subject(s)
Nanoparticles , Photoacoustic Techniques , Plaque, Atherosclerotic , Pneumonia , Animals , Mice , Plaque, Atherosclerotic/diagnostic imaging , Pneumonia/diagnostic imaging , Polymers
3.
Int J Mol Sci ; 23(16)2022 Aug 22.
Article in English | MEDLINE | ID: mdl-36012757

ABSTRACT

Hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT) is considered to be an essential enzyme for regulating the biosynthesis and composition of lignin. To investigate the properties and function of ZjHCT4, the ZjHCT4 gene was cloned from Zoysia japonica with a completed coding sequence of 1284-bp in length, encoding 428 amino acids. The ZjHCT4 gene promoter has several methyl jasmonate (MeJA) response elements. According to analysis of expression patterns, it was up-regulated by MeJA, GA3 (Gibberellin), and SA (Salicylic acid), and down-regulated by ABA (Abscisic acid). Ectopic ZjHCT4 expression in creeping bentgrass causes excessive plant elongation. In addition, the content of G-lingnin and H-lingnin fell in transgenic plants, whereas the level of S-lingnin increased, resulting in a considerable rise in the S/G unit ratio. Analysis of the expression levels of lignin-related genes revealed that the ectopic expression of ZjHCT4 altered the expression levels of a number of genes involved in the lignin synthesis pathway. Simultaneously, MeJA, SA, GA3, IAA, BR (Brassinosteroid), and other hormones were dramatically enhanced in transgenic plants relative to control plants, whereas ABA concentration was significantly decreased. Expression of ZjHCT4 impacted lignin composition and plant growth via altering the phenylpropionic acid metabolic pathway and hormone response, as revealed by transcriptome analysis. HCTs may influence plant lignin composition and plant development by altering hormone content. These findings contributed to a deeper comprehension of the lignin synthesis pathway and set the stage for further investigation and application of the HCTs gene.


Subject(s)
Agrostis , Lignin , Agrostis/genetics , Coenzyme A/metabolism , Gene Expression Regulation, Plant , Hormones/metabolism , Lignin/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Quinic Acid/metabolism , Shikimic Acid/metabolism
4.
Hepatobiliary Pancreat Dis Int ; 20(2): 137-141, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32146076

ABSTRACT

BACKGROUND: The progress of liver diseases may not stop after viral eradication. This study aimed to provide data on long-term prognosis of patients with hepatitis C virus (HCV) infection who underwent pegylated interferon plus ribavirin (PR) regimen and achieved a sustained virological response 24 weeks post-treatment (SVR24). METHODS: Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up. Baseline characteristics were profiled. The incidence of hepatocellular carcinoma (HCC), progression of liver disease (increase in liver stiffness or occurrence of decompensated complication), and HCV recurrence was all monitored. The accumulative and annualized incidence rates (AIRs) of these adverse events were analyzed, and the risk factors were also examined. RESULTS: In total, 151 patients reached a median follow-up time of 103 weeks. Among them, two had an incidence of HCC during the surveillance with AIR of 0.68% (95% CI: 0.00-1.63%). Six patients showed progression of liver disease with AIR of 2.05% (95% CI: 0.42%-3.68%). Three patients who had risky behaviors encountered HCV reinfection. The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients, including HCC and progression of liver disease (AIR: 6.17% vs. 1.42%, P = 0.039). CONCLUSIONS: The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period, but the risk level was low. Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones. HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C , Liver Neoplasms , Antiviral Agents/adverse effects , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Drug Therapy, Combination , Follow-Up Studies , Hepacivirus/genetics , Hepatitis C/complications , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Humans , Interferon-alpha/adverse effects , Liver Cirrhosis/drug therapy , Liver Cirrhosis/epidemiology , Liver Neoplasms/drug therapy , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Polyethylene Glycols/adverse effects , Ribavirin/adverse effects
5.
J Am Chem Soc ; 141(17): 6955-6966, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30964284

ABSTRACT

Combinatorial chemo and gene therapy provides a promising way to cure drug-resistant cancer, since the codelivered functional nucleic acids can regulate drug resistance genes, thus restoring sensitivity of the cells to chemotherapeutics. However, the dramatic chemical and physical differences between chemotherapeutics and nucleic acids greatly hinder the design and construction of an ideal drug delivery system (DDS) to achieve synergistic antitumor effects. Herein, we report a novel approach to synthesize a nanosized DDS using drug-integrated DNA with antisense sequences (termed "chemogene") to treat drug-resistant cancer. As a proof of concept, floxuridine (F), a typical nucleoside analog antitumor drug, was incorporated in the antisense sequence in the place of thymine (T) based on their structural similarity. After conjugation with polycaprolactone, a spherical nucleic acid (SNA)-like two-in-one chemogene can be self-assembled, which possesses the capabilities of rapid cell entry without the need for a transfection agent, efficient downregulation of drug resistance genes, and chronic release of chemotherapeutics for treating the drug-resistant tumors in both subcutaneous and orthotopic liver transplantation mouse models.


Subject(s)
Antineoplastic Agents/therapeutic use , Drug Carriers/chemistry , Drug Resistance, Neoplasm/drug effects , Floxuridine/therapeutic use , Neoplasms/drug therapy , Oligonucleotides, Antisense/chemistry , Animals , Cell Line, Tumor , DNA/chemical synthesis , DNA/chemistry , DNA/genetics , Down-Regulation/drug effects , Drug Carriers/chemical synthesis , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lactones/chemical synthesis , Lactones/chemistry , Mice, Nude , Neoplasms/genetics , Neoplasms/pathology , Oligonucleotides, Antisense/chemical synthesis , Oligonucleotides, Antisense/genetics , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/chemistry , Proof of Concept Study
6.
Small ; 15(47): e1903208, 2019 11.
Article in English | MEDLINE | ID: mdl-31617295

ABSTRACT

Cervical cancer treatment is subject to limited drug access to locally diseased targets and generally resistant to chemotherapy, thus it is essential to develop a local drug delivery system to overcome these problems, premised on guaranteeing drug efficacy. With this goal in mind, a multivalent interactions-based mucoadhesive nanogel for vaginal delivery is proposed. Briefly, the nanogel is constructed with mucoadhesive poly(acrylic acid) as the backbone and multiple inclusions between ß-cyclodextrin and paclitaxel as the crosslinking points. The in vitro experiments demonstrate that nanogel exerts high cytotoxicity to cancer cells, reverses multidrug resistance effectively, and successfully promotes the permeation of drugs. More to the point, as proved in the in vivo experiments, the retention time in the vagina is prolonged and the tumor growth is effectively suppressed by the nanogel without any side effects in the orthotopic cervical cancer model. As mentioned above, this novel mucoadhesive nanogel is believed to be a useful tool toward designing drug delivery systems for cervical cancer treatment.


Subject(s)
Mucus/chemistry , Nanogels/chemistry , Paclitaxel/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Acrylic Resins/chemical synthesis , Acrylic Resins/chemistry , Adhesiveness , Animals , Cell Death/drug effects , Cell Line, Tumor , Cell Membrane Permeability/drug effects , Cell Proliferation/drug effects , Disease Models, Animal , Drug Liberation , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Endocytosis/drug effects , Female , Humans , Mice, Inbred BALB C , Mice, Nude , Mucins/chemistry , Nanogels/ultrastructure , Paclitaxel/pharmacology , Solubility , Uterine Cervical Neoplasms/pathology , beta-Cyclodextrins/chemistry
7.
Cardiovasc Diabetol ; 17(1): 114, 2018 08 14.
Article in English | MEDLINE | ID: mdl-30107794

ABSTRACT

BACKGROUND: To improve outcomes in patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention remain an unmet clinical need. The study aimed to evaluate the efficacy and safety of G2-DESs and BP-DESs in patients with and without DM in a single center in China. METHODS: A total of 7666 consecutive patients who exclusively had G2-DES or BP-DES implantation throughout 2013 in our center were studied. The primary efficacy endpoint was any target lesion revascularization (TLR), whereas the primary safety endpoint was a composite of death or myocardial infarction (MI) at 2-year follow-up. RESULTS: G2-DESs had a similar occurrence of death, non-fatal MI, TLR, stroke, and stent thrombosis compared with BP-DESs in patients with DM (all P > 0.05). The incidence of TVR and TLR was lower for G2-DESs than for BP-DESs in patients without DM (3.2% vs. 5.1%, P = 0.002; 2.2% vs. 4.5%, P < 0.001, respectively). Kaplan-Meier analysis also showed better TVR- and TLR-free survival rates for G2-DESs than for BP-DESs in patients without DM. Multivariate analysis showed that a BP-DES was an independent risk factor for TLR (hazard ratio 1.963, 95% confidence interval 1.390-2.772, P < 0.001) in patients without DM, which was not predictive of other components of major adverse cardiac events (P > 0.05). CONCLUSIONS: G2-DESs have better efficacy, represented by a reduced risk of TLR, and similar safety compared with BP-DESs in patients without DM. G2-DESs have similar efficacy and safety compared with BP-DESs in patients with DM at 2-year follow-up.


Subject(s)
Absorbable Implants , Cardiovascular Agents/administration & dosage , Coronary Artery Disease/surgery , Diabetes Mellitus/epidemiology , Drug-Eluting Stents , Percutaneous Coronary Intervention/instrumentation , Polymers/chemistry , China/epidemiology , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Humans , Incidence , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Prospective Studies , Prosthesis Design , Recurrence , Risk Factors , Stroke/etiology , Time Factors , Treatment Outcome
8.
Angew Chem Int Ed Engl ; 57(12): 3064-3068, 2018 03 12.
Article in English | MEDLINE | ID: mdl-29364558

ABSTRACT

Functional siRNAs are employed as cross-linkers to direct the self-assembly of DNA-grafted polycaprolactone (DNA-g-PCL) brushes to form spherical and nanosized hydrogels via nucleic acid hybridization in which small interfering RNAs (siRNAs) are fully embedded and protected for systemic delivery. Owing to the existence of multivalent mutual crosslinking events inside, the crosslinked nanogels with tunable size exhibit not only good thermostability, but also remarkable physiological stability that can resist the enzymatic degradation. As a novel siRNA delivery system with spherical nucleic acid (SNA) architecture, the crosslinked nanogels can assist the delivery of siRNAs into different cells without any transfection agents and achieve the gene silencing effectively both in vitro and in vivo, through which a significant inhibition of tumor growth is realized in the anticancer treatment.


Subject(s)
DNA/chemistry , Drug Delivery Systems , Neoplasms, Experimental/drug therapy , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , RNA, Small Interfering/administration & dosage , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , HeLa Cells , Humans , Mice , Nanogels , Neoplasms, Experimental/pathology , Polyesters/chemistry , RNA, Small Interfering/chemistry , RNA, Small Interfering/pharmacology , RNA, Small Interfering/therapeutic use
9.
Analyst ; 141(10): 2940-7, 2016 05 10.
Article in English | MEDLINE | ID: mdl-27045202

ABSTRACT

In this work we report the use of inkjet printing as a precise and convenient means for microscale cell patterning in microfluidic chips followed by cell co-culture, stimulation and analysis. A self-made inkjet printing device was manufactured with adjustable parameters, which was capable of multiple cell printing within biocompatible materials. Sodium alginate was used as a printing matrix for cell encapsulation, and precisely distributed cell arrays on glass slides were obtained by accurate software controlled printing. By covering a PDMS layer with the corresponding microchannels onto the cell array substrate and subsequently injecting an ion cross-linking reagent, the cells containing alginate arrays gelated immediately and were immobilized on the bottom of the microchip, which could be utilized for cell culture and analysis. HepG2 cells and U251 cells were successfully co-patterned in the microchip and used for drug metabolism and diffusion experiment to imitate the in vivo situation, as a means to ascertain the capability of the system for precise microscale cell patterning in a microchip. The prodrug tegafur was metabolized by HepG2 cells into the active anticancer compound 5-fluorouracil and this produced an adverse gradient effect on U251 cells according to the distance from the HepG2 cells. The developed approach presented a feasible way to integrate inkjet cell printing and microfluidic chips for the first time, which is proved to be capable of spatially controlled printing of multiple kinds of cells into a microchip for cell culture, stimulation and analysis, which could be applied to tissue engineering, drug testing and related areas. We envision that the approach will help significantly increase the cell patterning efficacy in microfluidic chips as well as reduce the extent of laborious experimental work.


Subject(s)
Biocompatible Materials , Coculture Techniques , Microfluidics , Printing , Hep G2 Cells , Humans
10.
Nanotechnology ; 25(33): 335101, 2014 Aug 22.
Article in English | MEDLINE | ID: mdl-25073730

ABSTRACT

We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4ß-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4ß-aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC50) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indicated that this drug conjugate could selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD-I/PTX. We are convinced that these multifunctional drug conjugate micelles have tremendous potential for targeted cancer therapy.


Subject(s)
Antineoplastic Agents/chemistry , Drug Delivery Systems/methods , Micelles , Polymers/chemistry , Animals , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Male , Mice , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Tissue Distribution
11.
Zhonghua Gan Zang Bing Za Zhi ; 21(5): 345-7, 2013 May.
Article in Zh | MEDLINE | ID: mdl-24025134

ABSTRACT

To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Adult , Autoantibodies/blood , Drug Therapy, Combination , Female , Hepatitis C, Chronic/blood , Humans , Male , Recombinant Proteins/therapeutic use , Treatment Outcome
12.
Biomater Sci ; 11(8): 2639-2660, 2023 Apr 11.
Article in English | MEDLINE | ID: mdl-36790251

ABSTRACT

Repair and regeneration of tissues after injury are complex pathophysiological processes. Microbial infection, malnutrition, and an ischemic and hypoxic microenvironment in the injured area can impede the typical healing cascade. Distinguished by biomimicry of the extracellular matrix, high aqueous content, and diverse functions, hydrogels have revolutionized clinical practices in tissue regeneration owing to their outstanding hydrophilicity, biocompatibility, and biodegradability. Various hydrogels such as smart hydrogels, nanocomposite hydrogels, and acellular matrix hydrogels are widely used for applications ranging from bench-scale to an industrial scale. In this review, some emerging hydrogels in the biomedical field are briefly discussed. The protective roles of hydrogels in wound dressings and their diverse biological effects on multiple tissues such as bone, cartilage, nerve, muscle, and adipose tissue are also discussed. The vehicle functions of hydrogels for chemicals and cell payloads are detailed. Additionally, this review emphasizes the particular characteristics of hydrogel products that promote tissue repair and reconstruction such as anti-infection, inflammation regulation, and angiogenesis.


Subject(s)
Cartilage , Hydrogels , Hydrogels/chemistry , Wound Healing , Nanogels , Extracellular Matrix/chemistry
13.
ACS Appl Mater Interfaces ; 14(17): 19226-19240, 2022 May 04.
Article in English | MEDLINE | ID: mdl-35446537

ABSTRACT

The competition between cells integration and bacterial colonization determines the fate of implantations. To reveal the effects of clinical implant topographies on osteoblast differentiation and bacterial biofilm formation, a series of micron/submicron/nano-hierarchical structures were created at pure titanium surfaces (Ti-I, Ti-II, Ti-III). It was found that the hierarchical structures promoted MC3T3-E1 cell differentiation through contact guidance and Ti-II processed the best osteogenic ability. Undesirably, hierarchical surfaces further accelerated the biofilm formation due to submicron structures with low interaction. To reduce the risk of bacterial infections, hierarchical structures were prepared on the antibacterial Cu-bearing titanium alloy surfaces (TiCu-I, TiCu-II, TiCu-III). Hierarchical topographies not only endowed TiCu surfaces with antibacterial trapping characteristics due to CuO doped in the outermost oxides layer but also shifted the corrosion behavior of TiCu alloy into activation-passivation, increasing the Cu-ion release rate and further promoting the osteogenic differentiation. TiCu-III possessed excellent antibacterial trapping ability and optimal osteogenic action. Finally, in the osteomyelitis-modeled mice, hierarchical topographies aggravated the bacterial infection around Ti implants, which entirely lost the osseointegration, while all of the TiCu surfaces significantly inhibited the infection and accelerated the formation of new bone tunnels around the implants. In vivo studies successfully confirmed the tuning mechanism of hierarchical topographies on the biological responses of bacteria and cells to the Ti and TiCu alloys, which would pave the way to develop novel biofunctionalized metal implants.


Subject(s)
Alloys , Bacterial Infections , Alloys/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria , Mice , Osseointegration , Osteogenesis , Surface Properties , Titanium/chemistry , Titanium/pharmacology
14.
Biomed Mater ; 17(6)2022 Oct 06.
Article in English | MEDLINE | ID: mdl-36130606

ABSTRACT

Tissue development deformity or tissue defect is a major clinical challenge. Tissue engineering technology provides a promising solution to these problems. Among them, functional biomaterials with regenerative abilities are one of the development trends. Polypeptide is a small molecule that can be used to modify tissue engineering materials. However, the function of a single polypeptide molecule is limited and insufficient to construct comprehensive microenvironment for tissue regeneration. Fusion peptides combining two or more polypeptide molecules with different functions were expected to achieve multiple efficaciesin vivo, providing a novel solution for clinical tissue regeneration engineering applications. This paper reviews the construction methods, degradation process, and biological activities of fusion peptides, and presents recent global research progress and prospects concerning fusion peptides. It provides a reference helping to guide the future exploration and development of fusion peptide-based functional biomaterials for tissue engineering.


Subject(s)
Biocompatible Materials , Tissue Engineering , Biocompatible Materials/chemistry , Peptides , Wound Healing
15.
Chem Sci ; 12(35): 11740-11747, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34659710

ABSTRACT

Nucleic acid sensors have realized much success in detecting positively charged and neutral molecules, but have rarely been applied for measuring negatively charged molecules, such as fluoride, even though an effective sensor is needed to promote dental health while preventing osteofluorosis and other diseases. To address this issue, we herein report a quantitative fluoride sensor with a portable fluorometer readout based on fluoride riboswitch-regulated transcription coupled with CRISPR-Cas13-based signal amplification. This tandem sensor utilizes the fluoride riboswitch to regulate in vitro transcription and generate full-length transcribed RNA that can be recognized by CRISPR-Cas13a, triggering the collateral cleavage of the fluorophore-quencher labeled RNA probe and generating a fluorescence signal output. This tandem sensor can quantitatively detect fluoride at ambient temperature in aqueous solution with high sensitivity (limit of detection (LOD) ≈ 1.7 µM), high selectivity against other common anions, a wide dynamic range (0-800 µM) and a short sample-to-answer time (30 min). This work expands the application of nucleic acid sensors to negatively charged targets and demonstrates their potential for the on-site and real-time detection of fluoride in environmental monitoring and point-of-care diagnostics.

16.
J Hazard Mater ; 417: 126007, 2021 09 05.
Article in English | MEDLINE | ID: mdl-33992007

ABSTRACT

Microplastics (MPs) in marine and terrestrial environments have been intensively studied, but the dynamics of airborne MPs remains limited. Existing studies on atmospheric MPs are mostly derived from collection of atmospheric deposition, whereas direct measurements of airborne MPs are scarce. However, the abundance of airborne MPs is more relevant for evaluating human inhalation exposure risk. Herein, airborne MPs in indoor and outdoor environments from urban and rural areas of a coastal city in eastern China were investigated. MP concentrations (mean±SD) in indoor air (1583 ± 1180 n/m3) were an order of magnitude higher than outdoor air (189 ± 85 n/m3), and airborne MP concentrations in urban areas (224 ± 70 n/m3) were higher than rural areas (101 ± 47 n/m3). MPs smaller than 100 µm dominated airborne MPs, and the predominant shape of airborne MPs was fragments, as opposed to fibers. The larger MP size fractions contained a higher proportion of fibers, whereas the smaller size fractions were nearly exclusively composed of fragments. The health risk caused by ubiquitous airborne MPs should not be discounted as the maximum annual outdoor exposure of airborne MPs can reach 1 million/year, while indoor exposure may be even higher due to higher indoor airborne MP concentrations.


Subject(s)
Air Pollution, Indoor , Microplastics , Air Pollution, Indoor/analysis , China , Cities , Environmental Monitoring , Humans , Plastics
17.
Biochem Biophys Res Commun ; 387(4): 641-5, 2009 Oct 02.
Article in English | MEDLINE | ID: mdl-19607804

ABSTRACT

The transcription regulator CITED2 (CBP/p300-Interacting-Transactivator-with-ED-rich-tail-2) is known to suppress genes mediating angiogenesis and extracellular matrix (ECM) remodeling. However, it is unclear whether CITED2 has a role in controlling skeletal repair or remodeling. We tested the hypothesis that CITED2 functions in bone fracture healing by suppressing the expression of genes critical to ECM remodeling, angiogenesis and osteogenesis, importantly the matrix metalloproteinases (MMPs). Three hours following mandibular osteotomy or sham surgery of adult rats, osteotomy fronts were harvested and the expression of CITED2 and genes associated with fracture healing was ascertained by quantitative PCR. In parallel, gain-of-function studies examined the effect of overexpressing CITED2 on the expression and activity of several MMPs. In the fractured mandible, CITED2 expression was inversely related to the expression of MMP-2, -3, -9, -13, VEGF, HIF-1alpha, M-CSF, RANK-L, and OPG. Consistent with this, the over-expression of CITED2 in osteoblasts inhibited the expression and activity of MMP-2, -3, -9, and -13. Taken together, the studies suggest that CITED2 is a critical upstream regulator of fracture healing. The suppression of CITED2 early after fracture may allow an optimal initiation of the healing response.


Subject(s)
Fracture Healing/genetics , Gene Expression Regulation , Transcription Factors/metabolism , Animals , Extracellular Matrix/genetics , Extracellular Matrix/metabolism , Rats , Rats, Sprague-Dawley , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics
18.
ACS Appl Mater Interfaces ; 11(44): 41082-41090, 2019 Nov 06.
Article in English | MEDLINE | ID: mdl-31603313

ABSTRACT

Herein, we construct a structure-switchable gemcitabine (Ge)-containing DNA nanogel that can respond to the intracellular acidic environment, subsequently facilitating the chemodrug release inside the cells. Based on the structural similarity between Ge and deoxycytidine (dC), dC nucleotides in the component DNA strands used for nanogel assembly are fully replaced by Ge during their synthesis. By changing the designed sequences, two Ge-containing Y-shaped motifs with different sticky ends are first assembled and then associated together to form nanogel by sticky-end hybridizations. In particular, one of the sticky-end sequences is arbitrarily designed to be rich of Ge and the other is designed to be partially complementary to the first Ge-rich sticky end. At the neutral or basic condition, the Ge-rich sticky ends hybridize with the partially complementary sticky ends on the second Y motifs, keeping the assembled nanogel stable. Upon being exposed to the acidic condition, Ge-rich sticky ends intend to form intramolecular i-motif-like quadruplex structures, resulting in the disassembly of the nanogel. On the one hand, the nanosized feature enables the Ge-containing nanogel with rapid cellular uptake behavior. On the other hand, the pH-responsive feature endows the rapid disassembly of the nanogel to facilitate the enzymatic drug release inside the cell, resulting in the enhanced anticancer activity of the DNA-based drug delivery system.


Subject(s)
Antimetabolites, Antineoplastic/chemistry , DNA/chemistry , Deoxycytidine/analogs & derivatives , Drug Carriers/chemistry , Nanogels/chemistry , A549 Cells , Antimetabolites, Antineoplastic/metabolism , Antimetabolites, Antineoplastic/pharmacology , Apoptosis/drug effects , Carbocyanines/chemistry , Deoxycytidine/chemistry , Deoxycytidine/metabolism , Deoxycytidine/pharmacology , Drug Liberation , Endodeoxyribonucleases/metabolism , Fluorescence Resonance Energy Transfer , Humans , Hydrogen-Ion Concentration , Microscopy, Confocal , Gemcitabine
19.
Article in English | MEDLINE | ID: mdl-31083601

ABSTRACT

As emerging pollutants, microplastics have attracted the attention of scholars from all over the world. However, there is a lack of research on freshwater areas, even in densely populated urban areas. This study investigated eight urban lakes in Changsha, China. It was found that microplastic concentrations ranged from 2425 ± 247.5 items/m3 to 7050 ± 1060.66 items/m3 in the surface water of research areas and the maximum concentration was found in Yuejin Lake, a tourist spot in the center of the city. Anthropogenic factors are an important reason for microplastic abundance in urban lakes. The major shape of microplastics was linear and most of the microplastics were transparent. More than 89.5% of the microplastics had a size of less than 2 mm. Polypropylene was the dominant type in the studied waters. This study can provide a valuable reference for a better understanding of microplastic pollution in urban areas of China.


Subject(s)
Environmental Monitoring , Lakes/analysis , Plastics/analysis , Water Pollutants, Chemical/analysis , China , Cities , Water Pollution, Chemical/analysis
20.
Chem Commun (Camb) ; 55(46): 6603-6606, 2019 Jun 04.
Article in English | MEDLINE | ID: mdl-31119252

ABSTRACT

To overcome the slow activation of gemcitabine, we synthesized a DNA-like polygemcitabine (Ge10) strand through solid-phase synthesis, which not only undergoes rapid intracellular degradation to generate active gemcitabine derivatives, but can also self-assemble into nanogels through molecular recognition, rendering them as promising self-delivered nanodrugs for cancer therapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Deoxycytidine/analogs & derivatives , Gels/therapeutic use , Neoplasms/drug therapy , Polymers/therapeutic use , Prodrugs/therapeutic use , A549 Cells , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/toxicity , Apoptosis , Deoxycytidine/chemical synthesis , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Deoxycytidine/toxicity , Gels/chemical synthesis , Gels/pharmacology , Gels/toxicity , Humans , Mice, Nude , Nanoparticles/therapeutic use , Nanoparticles/toxicity , Polymers/chemical synthesis , Polymers/pharmacology , Polymers/toxicity , Prodrugs/chemical synthesis , Prodrugs/pharmacology , Prodrugs/toxicity , Xenograft Model Antitumor Assays , Gemcitabine
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