RESUMEN
Tetrachloroethylene (PCE) is a widely utilized volatile chemical in industrial applications, including dry cleaning and metal degreasing. Exposure to PCE potentially presents a significant health risk to workers as well as communities near contamination sites. Adverse health effects arise not only from PCE, but also from PCE degradation products, such as trichloroethylene (TCE) and vinyl chloride (VC). PCE, TCE, and VC can contaminate water, soil, and air, leading to exposure through multiple pathways, including inhalation, ingestion, and dermal contact. This study focused on a community setting in Martinsville, Indiana, a working-class Midwestern community in the United States, where extensive PCE contamination has occurred due to multiple contamination sites (referring to 'plumes'), including a Superfund site. Utilizing proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS), PCE, TCE, and VC concentrations were measured in the exhaled breath of 73 residents from both within and outside the plume areas. PCE was detected in 66 samples, TCE in 26 samples, and VC in 68 samples. Our results revealed a significant positive correlation between the concentrations of these compounds in exhaled breath and indoor air (Pearson correlation coefficients: PCE = 0.75, TCE = 0.71, and VC = 0.89). This study confirms the presence of PCE and its degradation products in exhaled breath in a community exposure investigation, demonstrating the potential of using exhaled breath analysis in monitoring exposure to environmental contaminants. This study showed the feasibility of utilizing PTR-TOF-MS in community investigations to assess exposure to PCE and its degradation products by measuring these compounds in exhaled breath and indoor air.
Asunto(s)
Contaminación del Aire Interior , Pruebas Respiratorias , Tetracloroetileno , Humanos , Pruebas Respiratorias/métodos , Contaminación del Aire Interior/análisis , Tetracloroetileno/análisis , Masculino , Femenino , Adulto , Espiración , Persona de Mediana Edad , Exposición a Riesgos Ambientales/análisis , Indiana , Monitoreo del Ambiente/métodosRESUMEN
Using natural clinoptilolite (NCP) as a carrier and alginate (Alg)-calcium as an active species, the porous silicon calcium alginate nanocomposite (Alg-Ca-NCP) was successfully fabricated via adsorption-covalence-hydrogen bond. Its structural features and physicochemical properties were detailed investigated by various characterizations. The results indicated that Alg-Ca-NCP presented the disordered lamellar structures with approximately uniform particles in size of 300-500 nm. Specially, their surface fractal evolutions between the irregular roughness and dense structures were demonstrated via the SAXS patterns. The results elucidated that the abundant micropores of NCP were beneficial for unrestricted diffusing of Alg-Ca, which was conducive to facilitate a higher loading and sustainable releasing. The Ca content of leaf mustard treated with Alg-Ca-NCP-0.5 was 484.5 mg/100g on the 21st day, higher than that by water (CK) and CaCl2 solution treatments, respectively. Meanwhile, the prepared Alg-Ca-NCPs presented the obvious anti-aging effects on peroxidase drought stress of mustard leaves. These demonstrations provided a simple and effective method to synthesize Alg-Ca-NCPs as delivery nanocomposites, which is useful to improve the weak absorption and low utilization of calcium alginate by plants.
Asunto(s)
Alginatos , Planta de la Mostaza , Zeolitas , Alginatos/química , Alginatos/farmacología , Zeolitas/química , Zeolitas/farmacología , Planta de la Mostaza/metabolismo , Planta de la Mostaza/efectos de los fármacos , Planta de la Mostaza/química , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/química , Porosidad , Brassica/metabolismo , Brassica/efectos de los fármacos , Brassica/crecimiento & desarrollo , Ácido Glucurónico/química , Nanocompuestos/química , Difracción de Rayos X , Ácidos Hexurónicos/química , Ácidos Hexurónicos/metabolismoRESUMEN
Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride (MA) and dopamine modified gelatin (GelMA-DA) are loaded with chondroitin sulfate (CS) (the obtained microgel named GC Ms) or bioactive glass (BG) (the obtained microgel named GB Ms), respectively. GC Ms and GB Ms show good biocompatibility with BMSCs, which suggested by the adhesion and proliferation of BMSCs on their surfaces. Specially, GC Ms promote chondrogenic differentiation of BMSCs, while GB Ms promote osteogenic differentiation. Furthermore, the injectable GC Ms and GB Ms are assembled integrally by bottom-up in situ cross-linking to obtain modular microgel-based bioassembly scaffold (GC-GB/HM), which show a distinct bilayer structure and good porous properties and swelling properties. Particularly, the results of in vivo and in vitro experiments show that GC-GB/HM can simultaneously regulate the expression levels of chondrogenic- and osteogenesis-related genes and proteins. Therefore, modular microgel-based assembly scaffold in this work with the ability to promote bidirectional differentiation of BMSCs and has great potential for application in the minimally invasive treatment of osteochondral tissue defects.
Asunto(s)
Diferenciación Celular , Condrogénesis , Células Madre Mesenquimatosas , Microgeles , Osteogénesis , Andamios del Tejido , Osteogénesis/efectos de los fármacos , Andamios del Tejido/química , Diferenciación Celular/efectos de los fármacos , Condrogénesis/efectos de los fármacos , Animales , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Microgeles/química , Gelatina/química , Gelatina/farmacología , Conejos , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Proliferación Celular/efectos de los fármacos , Ingeniería de Tejidos/métodosRESUMEN
Osteoarthritis (OA), primarily characterized by the deterioration of articular cartilage, is a highly prevalent joint-disabling disease. The pathological onset and progression of OA are closely related to cartilage lubrication dysfunction and synovial inflammation. Synergistic options targeted at restorative lubrication and anti-inflammation are expected to be the most attractive candidates to treat OA and perhaps help prevent it. Herein, a bioinspired lubricant (HA/PA@Lipo) was fabricated by combining anionic hyaluronan-graft-poly(2-acrylamide-2-methylpropanesulfonic acid sodium salt) (HA/PA) with cationic liposomes (Lipo) via electrostatic interaction. HA/PA@Lipo mimicked the lubrication complex located on the outer cartilage surface and was endowed cartilage with excellent cartilage-lubricating performances. After the antioxidant gallic acid (GA) was loaded for dual functionality, HA/PA@Lipo-GA was prepared with added anti-inflammatory properties. HA/PA@Lipo-GA showed favorable biocompatibility with C28/I2 cells, inhibited the production of reactive oxygen, and regulated the expression levels of anabolic genes and proteins. The therapeutic effects of HA/PA@Lipo-GA were evaluated using a sodium iodoacetate-induced OA rat model, and the preventive effects of HA/PA@Lipo-GA were estimated in vivo. The results suggested the robust potential of HA/PA@Lipo-GA with dual functions as a candidate option for OA treatment and prevention.
RESUMEN
PURPOSE: Doxorubicin (Dox) is clinically limited due to its dose-dependent cardiotoxicity. Andrographolide (Andro) has been confirmed to exert cardiovascular protective activities. This study aimed to investigate protective effects of Andro in Dox-induced cardiotoxicity (DIC). METHODS: The cardiotoxicity models were induced by Dox in vitro and in vivo. The viability and apoptosis of H9c2 cells and the myocardial function of c57BL/6 mice were accessed with and without Andro pretreatment. Network pharmacology and RNA-seq were employed to explore the mechanism of Andro in DIC. The protein levels of Bax, Bcl2, NLRP3, Caspase-1 p20, and IL-1ß were qualified as well. RESULTS: In vitro, Dox facilitated the downregulation of cell viability and upregulation of cell apoptosis, after Andro pretreatment, the above symptoms were remarkably reversed. In vivo, Andro could alleviate Dox-induced cardiac dysfunction and apoptosis, manifesting elevation of LVPWs, LVPWd, EF% and FS%, suppression of CK, CK-MB, c-Tnl and LDH, and inhibition of TUNEL-positive cells. Using network pharmacology, we collected and visualized 108 co-targets of Andro and DIC, which were associated with apoptosis, PI3K-AKT signaling pathway, and others. RNA-seq identified 276 differentially expressed genes, which were enriched in response to oxidative stress, protein phosphorylation, and others. Both network pharmacology and RNA-seq analysis identified Tap1 and Timp1 as key targets of Andro in DIC. RT-QPCR validation confirmed that the mRNA levels of Tap1 and Timp1 were consistent with the sequenced results. Moreover, the high expression of NLRP3, Caspase-1 p20, and IL-1ß in the Dox group was reduced by Andro. CONCLUSIONS: Andro could attenuate DIC through suppression of Tap1 and Timp1 and inhibition of NLRP3 inflammasome activation, serving as a promising cardioprotective drug.
RESUMEN
Cartilage has a limited ability to repair itself, highlighting the urgent need for suitable materials for cartilage regeneration. Achieving a balance between cell survival environment and hydrogel crosslinking density is crucial for photosensitive cell-laden cartilage repair materials to achieve both high strength and good cell viability. Here, an interpenetrating hydrogel consisted of methacrylate gelatin (GelMA) and glycidyl methacrylate silk fibroin (SG) was introduced. Compared to GelMA hydrogel, GelMA/SG had desired mechanical properties, with achieving up to 5 times of compression modulus and 6 times of compression failure energy. Meanwhile, the chondrocytes inside GelMA/SG exhibited great viability which was over 90 %. GelMA/SG as a bioink had favorable printability for digital light processing (DLP) bioprinting. The mesh DLP-printed scaffolds with high precision were created and GelMA/SG had a better shape retention ability than GelMA. Moreover, GelMA/SG cell-laden scaffolds had high strength while chondrocytes proliferated significantly in vitro culture. They were implanted under the skin of nude mice to evaluate ectopic chondrogenesis in vivo. The GelMA/SG cell-laden scaffolds indicated little deformation and high expression of collagen type II and glycosaminoglycans, which was advantageous for cartilage regeneration. The scaffold and its fabrication strategy provide potential solutions for clinical cartilage repair problems in the future.
Asunto(s)
Bioimpresión , Ingeniería de Tejidos , Animales , Ratones , Andamios del Tejido , Ratones Desnudos , Cartílago , Hidrogeles , Impresión Tridimensional , GelatinaRESUMEN
Concerns about chemical exposure in the electronics manufacturing industry have long been recognized, but data are lacking in Southeast Asia. We conducted a study in Batam, Indonesia, to evaluate chemical exposures in electronics facilities, using participatory research and biological monitoring approaches. A convenience sample of 36 workers (28 exposed, 8 controls) was recruited, and urine samples were collected before and after shifts. Five solvents (acetone, methyl ethyl ketone, toluene, benzene, and xylenes) were found in 46%-97% of samples, and seven metals (arsenic, cadmium, cobalt, tin, antimony, lead, and vanadium) were detected in 60%-100% of samples. Biological monitoring and participatory research appeared to be useful in assessing workers' exposure when workplace air monitoring is not feasible due to a lack of cooperation from the employer. Several logistical challenges need to be addressed in future biomonitoring studies of electronics workers in Asia in factories where employers are reluctant to track workers' exposure and health.
Asunto(s)
Contaminantes Ocupacionales del Aire , Exposición Profesional , Humanos , Solventes/análisis , Exposición Profesional/análisis , Monitoreo Biológico , Indonesia , Monitoreo del AmbienteRESUMEN
PURPOSE: Trastuzumab is a landmark agent in the treatment of human epidermal growth factor receptor-2(HER2)-positive breast cancer. Nevertheless, trastuzumab also comes with unexpected cardiac side effects. Hyperoside is a natural product that serves beneficial roles in cardiovascular disease. This study aimed to explore the effect and mechanism of hyperoside in trastuzumab-induced cardiotoxicity. METHODS: A female C57BL/6 mice cardiotoxicity model was established via intraperitoneally injecting with trastuzumab (10 mg/kg/day, once every other day, cumulative dosage to 40 mg/kg) with or without hyperoside (15 or 30 mg/kg/day) administration. In vitro, the H9c2 cells were exposed to 1 µM trastuzumab with or without hyperoside (100 or 200 µM) administration. Cardiac function was evaluated by echocardiographic, myocardial enzymes levels, and pathological section examinations. TUNEL staining and Annexin V-FITC/ propidium iodide flow cytometry were used to analyze the cardiomyocyte apoptosis. RESULTS: Compared to the control group, the LVEF, LVFS was decreased and the concentrations of cTnT, CK, CK-MB and LDH in mice were significantly increased after treatment with trastuzumab. Collagen deposition and cardiomyocyte hypertrophy were observed in the myocardium of the trastuzumab group. However, these changes were all reversed by different doses of hyperoside. In addition, hyperoside attenuated trastuzumab-induced myocardium apoptosis and H9c2 cells apoptosis through inhibiting the expressions of cleaved caspase-3 and Bax. Trastuzumab abolished the PI3K/Akt signaling pathway in mice and H9c2 cells, while co-treatment of hyperoside effectively increased the ratio of p-Akt/Akt. CONCLUSION: Hyperoside inhibited trastuzumab-induced cardiotoxicity through activating the PI3K/Akt signaling pathway. Hyperoside may be a promising therapeutic approach to trastuzumab-induced cardiotoxicity.
RESUMEN
We aimed to explore the effects of single nucleotide polymorphisms (SNPs) in tropoelastin gene on tropoelastin mRNA and elastin expressions in human aortic smooth muscle cells (HASMCs). Two SNP loci, rs2071307 (G/A) and rs1785598 (G/C), were selected to construct recombinant lentivirus vectors carrying wild-type and mutant tropoelastin gene. Recombinant plasmids including pWSLV-02-ELN, pWSLV-02-ELN-mut1, and pWSLV-02-ELN-mut2 were constructed, before being amplified by polymerase chain reaction (PCR) and sequenced. The prepared plasmids and the packaging plasmids (pVSV-G and psPAX2) were cotransfected into HEK293T cells to obtain recombinant lentiviruses carrying tropoelastin gene. Afterward, HASMCs were infected with recombinant lentiviruses, and the positive cells sorted by flow cytometry were amplified. Four stable HASMCs cell lines including pWSLV-02-ELN, pWSLV-02-ELN-mut1, pWSLV-02-ELN-mut2, and pWSLV-02 vector were constructed. The expressions of tropoelastin mRNA and elastin in HASMCs were detected by real-time quantitative reverse transcription-PCR and western blot, respectively. Recombinant plasmids including pWSLV-02-ELN-mut1, pWSLV-02-ELN-mut2, and pWSLV-02-ELN were successfully constructed. Recombinant lentiviruses carrying tropoelastin gene were obtained via lentivirus packaging. After infection for 24 h, 3 days and 5 days in HASMCs, tropoelastin mRNA expressions in pWSLV-02-ELN-mut1 and pWSLV-02-ELN-mut2 groups were significantly lower than that of pWSLV-02-ELN group. Besides, after infection for 24 h, 3 days, and 5 days, elastin levels in pWSLV-02-ELN-mut1 and pWSLV-02-ELN-mut2 groups were significantly lower than that in pWSLV-02-ELN group. In conclusion, SNPs mutation of tropoelastin gene affected the expression of tropoelastin mRNA and elastin, suggesting that the polymorphisms of rs2071307 and rs17855988 in tropoelastin gene might be important factors for AD development.
Asunto(s)
Tropoelastina , Humanos , Elastina/genética , Elastina/metabolismo , Células HEK293 , Mutación , Miocitos del Músculo Liso/metabolismo , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , ARN Mensajero/metabolismo , Tropoelastina/genética , Tropoelastina/metabolismoRESUMEN
Local drug delivery via inter-articular injection offers a promising scenario to treat the most common joint disease, osteoarthritis (OA), which is closely associated with the increased friction or cartilage degeneration and the inflammatory syndrome of synovium. Therefore, it is quite necessary to improve the retention of drug delivery system within synovial joint, simultaneously restore the lubrication of degraded cartilage and meanwhile alleviate the inflammation. In this study, we propose a hydrophilic coating modified nano-liposome drug carrier (PMPC-Lipo) to achieve these functions. A modified chain transfer agent was utilized to polymerize 2-methacryloyloxyethyl phosphorylcholine (MPC), the obtained polymer, combined with lecithin and cholesterol, formed a liposome (PMPC-Lipo) where poly (MPC) acted as hydrophilic coating. PMPC-Lipo was found to restore the lubrication of mechanically damage cartilage (mimicking OA conditions) to the level like healthy cartilage due to the hydration lubrication. Additionally, due to the presence of poly (MPC), we also found PMPC-Lipo avoid the recognition of macrophage and thus escape from the phagocytosis to prolong its retention in synovial joint. Furthermore, after encapsulating gallic acid (GA) into PMPC-Lipo, the obtained GA-PMPC-Lipo can effectively scavenge reactive oxygen species and restore the imbalance of matrix secretion in inflammatory chondrocytes. Collectively, the proposed GA-PMPC-Lipo may provide a new idea for osteoarthritis treatment by providing both long-term effective drug action and excellent lubrication properties.
RESUMEN
Hydrogels are extensively investigated as biomimetic extracellular matrix (ECM) scaffolds in tissue engineering. The physiological properties of ECM affect cellular behaviors, which is an inspiration for cell-based therapies. Photocurable hyaluronic acid (HA) hydrogel (AHAMA-PBA) modified with 3-aminophenylboronic acid, sodium periodate, and methacrylic anhydride simultaneously is constructed in this study. Chondrocytes are then cultured on the surface of the hydrogels to evaluate the effect of the physicochemical properties of the hydrogels on modulating cellular behaviors. Cell viability assays demonstrate that the hydrogel is non-toxic to chondrocytes. The existence of phenylboronic acid (PBA) moieties enhances the interaction of chondrocytes and hydrogel, promoting cell adhesion and aggregation through filopodia. RT-PCR indicates that the gene expression levels of type II collagen, Aggrecan, and Sox9 are significantly up-regulated in chondrocytes cultured on hydrogels. Moreover, the mechanical properties of the hydrogels have a significant effect on the cell phenotype, with soft gels (≈2 kPa) promoting chondrocytes to exhibit a hyaline phenotype. Overall, PBA-functionalized HA hydrogel with low stiffness exhibits the best effect on promoting the chondrocyte phenotype, which is a promising biomaterial for cartilage regeneration.
Asunto(s)
Condrocitos , Ácido Hialurónico , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Hidrogeles/química , Ingeniería de Tejidos , FenotipoRESUMEN
Corneal scarring caused by epithelial-stromal injury impairs corneal transparency and visual acuity. Excess secretion of transforming growth factor-beta 1 (TGF-ß1), which promotes wound closure, penetrates the corneal stroma via defects in the epithelial basement membrane and induces the differentiation of corneal fibroblasts to myofibroblasts, leading to scar formation. Modulating TGF-ß1 penetration might alleviate corneal scar formation and restore transparency. In this study, sulfated hyaluronan (sHA) coatings were self-assembled above wounded corneal stroma to modulate TGF-ß1 penetration, and their ability to alleviate corneal scarring was investigated. The formation of sHA coatings was rapid (within 30 s), and the high-sulfated hyaluronan coating efficiently blocked penetration by TGF-ß1 and reduced the concentration of TGF-ß1 in the corneal stroma. Further investigation showed that the ability of TGF-ß1 to induce differentiation of corneal fibroblasts into myofibroblasts was inhibited by sHA binding. Evaluation of corneal scarring with sHA coating in a rabbit model of lamellar resection indicated that a sHA (high sulfation) coating effectively reduced scar formation. Immunohistochemical staining of α-smooth muscle actin and optical coherence tomography of the anterior segment showed minimal scar tissue formation in the sHA group. This work presents a promising alternative to alleviate scarring in corneal epithelial-stromal injury.
Asunto(s)
Lesiones de la Cornea , Factor de Crecimiento Transformador beta1 , Animales , Conejos , Factor de Crecimiento Transformador beta1/farmacología , Cicatriz/tratamiento farmacológico , Cicatriz/prevención & control , Ácido Hialurónico/farmacología , Sulfatos/farmacología , Lesiones de la Cornea/tratamiento farmacológico , FibroblastosRESUMEN
The synthesis of efficient, stable, and green multifunctional electrode materials is a long-standing challenge for modern society in the field of energy storage and conversion. To this end, we successfully synthesized five bimetallic precursor materials with excellent performance by hydrothermal reaction with the assistance of a high concentration of polyvinylpyrrolidone (PVP), and then, sulfide etched the lamellar precursor materials among them to obtain the one-dimensional heterostructured samples. Benefiting from the synergistic effect of the bimetal and the continuous electron/ion transport structure, the samples displayed excellent bifunctional activity in supercapacitor and oxygen evolution reaction (OER). Regarding supercapacitors, the exceptional performance of 2817.2 F g-1 at 1 A g-1 was demonstrated, while the asymmetric supercapacitors made showed an extraordinary energy density of 150.2 Wh kg-1 at a power density of 618.5 W kg-1 and outstanding cycling performance (94.74% capacity retention after 20,000 cycles at 10 A g-1). Simultaneously, a wearable flexible electrode that can be wrapped around a finger was coated on a carbon cloth and was found to light up a 0.5-m-long strip of light. Moreover, it exhibited an ultralow oxygen reduction overpotential of 249 mV at 10 mA cm-2. Hence, our work provides a facile strategy to modulate the synthesis of heterogeneous structured sulfides with a continuous electron/ion transport pathway, which possesses excellent oxygen reduction electrocatalytic performance while meeting superior supercapacitor performance. Such work provides an effective approach for the construction of multifunctional electrochemical energy materials.
Asunto(s)
Carbono , Oxígeno , Electrodos , Transporte de Electrón , Sulfuros , AzufreRESUMEN
Osteochondral defects threaten the quality of life of patients to a great extent. To simulate gradient changes in osteochondral tissue, a gradient-mixing injection device consisting of a controller and injection pumps is design. Bioactive glass (BG) and gellan gum (GG) are used to prepare thermosensitive injectable gradient hydrogels (B0.5 G, B1 G) with an upper critical solution temperature (UCST) range of 37.7-40.2 °C using this device for the first time. The mechanical properties of gradient hydrogels are significantly better than those of pure GG hydrogels. The gradients in the composition, structure, and morphology of gradient hydrogels are confirmed via physicochemical characterization. Cytocompatibility tests show that hydrogels, especially B0.5 G gradient hydrogels, promote the proliferation of bone marrow mesenchymal stem cells (BMSCs). Most importantly, qRT-PCR shows that the different components in B0.5 G gradient hydrogels simultaneously induce the osteogenic and chondrogenic differentiation of BMSCs. Experimental injection in porcine osteochondral defects indicates that the B0.5 G gradient hydrogel seamlessly fills irregular osteochondral defects in a less invasive manner by controlling the temperature to avoid cellular and tissue damage arising from crosslinkers or other conditions. These results show that thermosensitive injectable B0.5 G gradient hydrogels have the potential for less invasive integrated osteochondral repair.
Asunto(s)
Hidrogeles , Células Madre Mesenquimatosas , Animales , Porcinos , Hidrogeles/farmacología , Hidrogeles/química , Calidad de Vida , Diferenciación Celular , OsteogénesisRESUMEN
OBJECTIVES: Recently, it has been reported that cepharanthine (CEP) is highly likely to be an agent against Coronavirus disease 2019 (COVID-19). In the present study, a network pharmacology-based approach combined with RNA-sequencing (RNA-seq), molecular docking, and molecular dynamics (MD) simulation was performed to determine hub targets and potential pharmacological mechanism of CEP against COVID-19. METHODS: Targets of CEP were retrieved from public databases. COVID-19-related targets were acquired from databases and RNA-seq datasets GSE157103 and GSE155249. The potential targets of CEP and COVID-19 were then validated by GSE158050. Hub targets and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI) network analysis and enrichment analysis. Subsequently, molecular docking was carried out to predict the combination of CEP with hub targets. Lastly, MD simulation was conducted to further verify the findings. RESULTS: A total of 700 proteins were identified as CEP-COVID-19-related targets. After the validation by GSE158050, 97 validated targets were retained. Enrichment results indicated that CEP acts on COVID-19 through multiple pathways, multiple targets, and overall cooperation. Specifically, PI3K-Akt signaling pathway is the most important pathway. Based on PPI network analysis, 9 central hub genes were obtained (ACE2, STAT1, SRC, PIK3R1, HIF1A, ESR1, ERBB2, CDC42, and BCL2L1). Molecular docking suggested that the combination between CEP and 9 central hub genes is extremely strong. Noteworthy, ACE2, considered the most important gene in CEP against COVID-19, binds to CEP most stably, which was further validated by MD simulation. CONCLUSION: Our study comprehensively illustrated the potential targets and underlying molecular mechanism of CEP against COVID-19, which further provided the theoretical basis for exploring the potential protective mechanism of CEP against COVID-19.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Simulación de Dinámica Molecular , Humanos , Simulación del Acoplamiento Molecular , Enzima Convertidora de Angiotensina 2 , Farmacología en Red , Fosfatidilinositol 3-Quinasas , ARNRESUMEN
Articular cartilage provides ultralow friction to maintain the physiological function of the knee joint, which arises from the hierarchical complex composed of hyaluronic acid, phospholipids, and lubricin, covering the cartilage surface as boundary lubrication layers. Cartilage-lubricating polymers (HA/PA and HA/PM) mimicking this complex have been demonstrated to restore the lubrication of cartilage via hydration lubrication, thus contributing to the treatment of early osteoarthritis (OA) in vivo. Here, biomimetic cartilage-lubricating hydrogels (HPX/PVA) were constructed by blending HA/PA and HA/PM (HPX) with polyvinyl alcohol (PVA) to improve the boundary lubrication and wear properties, so that the obtained hydrogels may offer a solution to the main drawbacks of PVA hydrogels used as cartilage implants. The HPX/PVA hydrogels exhibited good physicochemical and mechanical properties through hydrogen-bonding interactions, and showed lower friction and wear under the boundary lubrication and fluid film lubrication mechanisms, which remained when the hydrogels were rehydrated. Our strategy may provide new insights into exploring cartilage-inspired lubricating hydrogels.
RESUMEN
Galactose, an important carbohydrate nutrient, is involved in several types of cellular metabolism, participating in physiological activities such as glycosaminoglycan (GAG) synthesis, glycosylation, and intercellular recognition. The regulatory effects of galactose on osteoarthritis have attracted increased attention. In this study, in vitro cell models of ATDC5 and chondrocytes were prepared and cultured with different concentrations of galactose to evaluate its capacity on chondrogenesis and cartilage matrix formation. The cell proliferation assay demonstrated that galactose was nontoxic to both ATDC5 cells and chondrocytes. RT-PCR and immunofluorescence staining indicated that the gene expressions of cartilage matrix type II collagen and aggrecan were significantly upregulated with increasing galactose concentration and the expression and accumulation of the extracellular matrix (ECM) protein. Overall, these results indicated that a galactose concentration below 8 mM exhibited the best effect on promoting chondrogenesis, which entitles galactose as having considerable potential for cartilage repair and regeneration.
RESUMEN
Atherosclerosis is the most common arterial disease and is closely related to vascular calcification. CircHIPK3 has been implicated in atherosclerosis development, but the possible downstream regulatory mechanisms remain unclear. The levels of circHIPK3, miR-106a and MFN2 in tissues and blood samples of patients with atherosclerosis were detected by RT-qPCR. The levels of circHIPK3, miR-106a and MFN2 were detected by RT-qPCR and the expression levels of MFN2, osteogenic and cartilage differentiation marker proteins were detected by western blot in vitro. ALP staining, Alizarin Red staining, and calcium content detection evaluated the degree of osteogenic differentiation of cells. Alcian blue staining detected the level of cell cartilage differentiation. Luciferase detected the targeting relationship between circHIPK3 and miR-106a-5p, as well as miR-106a-5p and MFN2. CircHIPK3 and MFN2 were low expressed and miR-106a-5p was highly expressed in tissues and blood samples of patients with atherosclerosis, as well as vascular smooth muscle cell (VSMC) with osteogenic and cartilage differentiation. Overexpression of circHIPK3 reduced the cell mineralization and calcium content. Overexpression of circHIPK3 inhibited osteogenic differentiation by decreasing ALP activity, RUNX2, and OPG expression, and increasing SM22α and SMA level. What's more, overexpression of circHIPK3 decreased the chondrogenic differentiation by inhibiting the protein level of SOX9, aggrecan, and collagen II. CircHIPK3 targeted miR-106a-5p and miR-106a-5p targeted MFN2. MiR-106a-5p overexpression or MFN2 depletion repressed the effect of circHIPK3 overexpression on VSMC calcification. CircHIPK3 regulated osteogenic and cartilage differentiation of VSMC via miR-106a-5p/MFN2 axis, indicating a target for treating vascular calcification.
Asunto(s)
Aterosclerosis , GTP Fosfohidrolasas , MicroARNs , ARN Circular , Calcificación Vascular , Humanos , Aterosclerosis/genética , Calcio , Diferenciación Celular , GTP Fosfohidrolasas/genética , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Mitocondriales/genética , Músculo Liso Vascular/metabolismo , Osteogénesis/genética , Calcificación Vascular/genética , ARN Circular/genéticaRESUMEN
Specific recognition and strong affinities of bacteria receptors with the host cell glycoconjugates pave the way to control the bacteria aggregation and kill bacteria. Herein, using aggregation-induced emission (AIE) molecules decorated upper critical solution temperature (UCST) polyvalent scaffold (PATC-GlcN), an approach toward visualizing bacteria aggregation and controlling bacteria-polyvalent scaffolds affinities under temperature stimulus is described. Polyvalent scaffolds with diblocks, one UCST block PATC of polyacrylamides showing a sharp UCST transition and typical AIE behavior, the second bacteria recognition block GlcN of hydrophilic glucosamine modified polyacrylamide, are prepared through a reversible addition and fragmentation chain transfer polymerization. Aggregated chain conformation of polyvalent scaffolds at temperature below UCST induces the aggregation of E. coli ATCC8739, because of the high density of glucosamine moieties, whereas beyond UCST, the hydrophilic state of the scaffolds dissociates the bacteria aggregation. The sweet-talking of bacteria toward the polyvalent scaffolds can be visualized by the fluorescent imaging technique, simultaneously. Due to the specific recognition of polyvalent scaffolds with bacteria, the photothermal agent IR780 loaded PATC-GlcN shows the targeted killing ability toward E. coli ATCC8739 in vitro and in vivo under NIR radiation.
Asunto(s)
Escherichia coli , Polímeros , Polimerizacion , TemperaturaRESUMEN
OBJECTIVE: This study aimed to analyze the application value of intracavitary electrocardiogram (ECG) classification in peripherally inserted central catheter (PICC) tip localization in patients with cancer. METHODS: Using a self-control study method, 325 patients with cancer underwent intracavitary ECGs to position the tip of a PICC catheter. The P wave, QRS wave amplitude, and waveform changes of each intracavitary ECG were recorded. Chest X-ray examination was performed after the catheterization to compare the results of different intracavity ECG maps with the results of the chest X-ray. RESULTS: The intracavitary ECG positioning maps of the 325 patients were divided into four categories: (1) increased P wave (293 cases), accounting for 90.15% (293/325) of all cases; compared with the positioning results of the chest X-rays, the placement rate was 98.98% (290/293); (2) negative deepening of the P wave (1 case), accounting for 0.31% (1/325) of all cases and with a placement rate of 100% (1/1); (3) no change in P wave (19 cases), accounting for 5.85% (19/325) of all cases and with a placement rate of 42.11% (8/19); (4) atrial fibrillation/atrial flutter (12 cases), accounting for 3.69% (12/325) of all cases and with a placement rate of 58.33% (7/12). The four types of intracavitary ECG positioning maps had statistically significant differences (χ2 = 133.924, P = 0.000). CONCLUSION: There are four types of intracavitary ECG localization maps: increased P wave, negative deepening of the P wave, no change in P wave, and atrial fibrillation/atrial flutter. The increased P wave pattern had the highest occurrence probability and high positioning accuracy. It therefore has strong clinical application value for PICC tip localization in patients with cancer.