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1.
Adv Healthc Mater ; : e2304125, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38301194

RESUMO

Disturbance in the mitochondrial electron transport chain (ETC) is a key factor in the emerging discovery of immune cell activation in inflammatory diseases, yet specific regulation of ETC homeostasis is extremely challenging. In this paper, a mitochondrial complex biomimetic nanozyme (MCBN), which plays the role of an artificial "VI" complex and acts as an electron and free radical conversion factory to regulate ETC homeostasis is creatively developed. MCBN is composed of bovine serum albumin (BSA), polyethylene glycol (PEG), and triphenylphosphine (TPP) hierarchically encapsulating MnO2 polycrystalline particles. It has nanoscale size and biological properties like natural complexes. In vivo and in vitro experiments confirm that MCBN can target the mitochondrial complexes of inflammatory macrophages, absorb excess electrons in ETC, and convert the electrons to decompose H2 O2 . By reducing the ROS and ATP bursts and converting existing free radicals, inhibiting NLRP3 inflammatory vesicle activation and NF-κB signaling pathway, MCBN effectively suppresses macrophage M1 activation and inflammatory factor secretion. It also demonstrates good inflammation control and significantly alleviates alveolar bone loss in a mouse model of ligation-induced periodontitis. This is the first nanozyme that mimics the mitochondrial complex and regulates ETC, demonstrating the potential application of MCBN in immune diseases.

2.
Phys Chem Chem Phys ; 26(8): 6524-6531, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38329237

RESUMO

This work presents mechanisms to rationalize the nature of ultrafast photochemical and photophysical processes on the first singlet metal-ligand charge transfer state (1MLCT1) of the [Ru(bpy)3]2+ complex. The 1MLCT1 state is the lowest-lying singlet excited state and the most important intermediate in the early evolution of photoexcited [Ru(bpy)3]2+*. The results obtained from simple but interpretable theoretical models show that the 1MLCT1 state can be very quickly formed via both direct photo-excitation and internal conversions and then can efficiently relax to its equilibrium geometry in ca. 5 fs. The interligand electron transfer (ILET) on the potential energy surface of the 1MLCT1 state is also extremely fast, with a rate constant of ca. 1.38 × 1013 s-1. The ultrafast ILET implies that the excited electron can dynamically delocalize over the three bpy ligands, despite the fact that the excited electron may be localized on either one of the three ligands at the equilibrium geometries of the three symmetric equivalent minima. Since rapid ILET essentially suggests delocalization, the long-standing controversy in inorganic photophysics-whether the excited electron is localized or delocalized-may therefore be calmed down to some extent.

3.
Redox Biol ; 67: 102922, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37826866

RESUMO

Clinical epidemiological studies have confirmed that tobacco smoking disrupts bone homeostasis and is an independent risk factor for the development of osteoporosis. The low viability and inferior osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) are important etiologies of osteoporosis. However, few basic studies have elucidated the specific mechanisms that tobacco toxins devastated BMSCs and consequently induced or exacerbated osteoporosis. Herein, our clinical data showed the bone mineral density (BMD) values of femoral neck in smokers were significantly lower than non-smokers, meanwhile cigarette smoke extract (CSE) exposure led to a significant decrease of BMD in rats and dysfunction of rat BMSCs (rBMSCs). Transcriptomic analysis and phenotype experiments suggested that the ferroptosis pathway was significantly activated in CSE-treated rBMSCs. Accumulated intracellular reactive oxygen species activated AMPK signaling, furtherly promoted NCOA4-mediated ferritin-selective autophagic processes, increased labial iron pool and lipid peroxidation deposition, and ultimately led to ferroptosis in rBMSCs. Importantly, in vivo utilization of ferroptosis and ferritinophagy inhibitors significantly alleviated BMD loss in CSE-exposed rats. Our study innovatively reveals the key mechanism of smoking-related osteoporosis, and provides a possible route targeting on the perspective of BMSC ferroptosis for future prevention and treatment of smoking-related bone homeostasis imbalance.


Assuntos
Ferroptose , Osteoporose , Ratos , Animais , Osteogênese , Osteoporose/etiologia , Ferro/metabolismo
4.
Microorganisms ; 11(8)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37630686

RESUMO

Porcine extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of death in pigs and has led to considerable economic losses for the pig industry. Porcine ExPEC infections often cause systemic inflammatory responses in pigs, characterized by meningitis, arthritis, pneumonia, and septicemia. Baicalin has been reported to possess potent anti-inflammatory activity, but its function in porcine ExPEC remains unknown. The aim of this study was to explore the protective effect and mechanism of baicalin against the porcine ExPEC-induced inflammatory responses in 3D4/21 cells. After treatment with baicalin, the effects on cell damage, the level of pro-inflammatory cytokines, the expression of nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathways, and the activation of NOD-like receptor protein 3 (NLRP3) inflammasomes were examined. Our results show that baicalin significantly reduced the damage to 3D4/21 cells infected with porcine ExPEC PCN033. Further study showed that baicalin significantly reduced the transcription and expression of pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-8 (IL-8). Furthermore, baicalin inhibited the phosphorylation of proteins such as P65, nuclear factor κB inhibitor α (IκBα), extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and P38 and reduced the expression levels of proteins such as NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. These results reveal that baicalin reduced the damage to 3D4/21 cells by inhibiting the expression of NF-κB/MAPK signaling pathways and blocking NLRP3 inflammasome activation in 3D4/21 cells infected with porcine ExPEC. Taken together, these results suggest that baicalin may have potential as a medicine for the treatment of porcine ExPEC-infected pigs by regulating inflammatory responses. This study provides a novel potential pharmaco-therapeutic approach to preventing porcine ExPEC infection.

5.
Analyst ; 148(15): 3666-3676, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37431281

RESUMO

Photoelectrochemical sensors have outstanding advantages including high sensitivity and miniaturization for outdoor use. Recently, perovskite quantum dots have attracted significant attention due to their high photoluminescence quantum yield. Nonetheless, there is still a strong need to improve their performance in challenging aqueous biological applications. In this paper, based on the molecularly imprinted polymer encapsulation of CsPbBr3 perovskite quantum dot/TiO2 inverse opal heterojunction structures, linear photoelectrochemical detection of cholesterol in aqueous solution was obtained without the involvement of an enzyme. The attenuation of photocurrent intensity under intermittent irradiation within 900 s (45 on/off cycles) was only 8.6%, demonstrating the superior stability of CsPbBr3 based sensor here. At the same time, the minimum detection limit of 1.22 × 10-9 mol L-1 in buffer conditions was lower than that reported for cholesterol photoelectric sensors. It has also been shown that the photoelectrochemical sensor of CsPbBr3 here outperformed that of CH3NH3PbBr3, which is another important member of the perovskite family. Finally, the proposed photoelectrochemical sensor platform was successfully applied in the determination of cholesterol in challenging serum with satisfactory recovery. The synergism among CsPbBr3 perovskite quantum dots, TiO2 inverse opal structure and imprinted polymer has led to greatly improved water stability, super selectivity and sensitivity, thus promoting the development of perovskite-based biological sensors.

6.
J Nanobiotechnology ; 21(1): 229, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37468894

RESUMO

The inflammatory immune environment surrounding titanium bone implants determines the formation of osseointegration, and nanopatterning on implant surfaces modulates the immune microenvironment in the implant region. Among many related mechanisms, the mechanism by which nanopatterning controls macrophage inflammatory response still needs to be elucidated. In this paper, we found that inhibition of the nuclear envelope protein lamin A/C by titania nanotubes (TNTs) reduced the macrophage inflammatory response. Knockdown of lamin A/C reduced macrophage inflammatory marker expression, while overexpression of lamin A/C significantly elevated inflammatory marker expression. We further found that suppression of lamin A/C by TNTs limited actin polymerization, thereby reducing the nuclear translocation of the actin-dependent transcriptional cofactor MRTF-A, which subsequently reduced the inflammatory response. In addition, emerin, which is a key link between lamin A/C and actin, was delocalized from the nucleus in response to mechanical stimulation by TNTs, resulting in reduced actin organization. Under inflammatory conditions, TNTs exerted favourable osteoimmunomodulatory effects on the osteogenic differentiation of mouse bone marrow-derived stem cells (mBMSCs) in vitro and osseointegration in vivo. This study shows and confirms for the first time that lamin A/C-mediated nuclear mechanotransduction controls macrophage inflammatory response, and this study provides a theoretical basis for the future design of immunomodulatory nanomorphologies on the surface of metallic bone implants.


Assuntos
Lamina Tipo A , Nanotubos , Camundongos , Animais , Actinas , Osteogênese , Mecanotransdução Celular , Macrófagos , Titânio/farmacologia , Propriedades de Superfície
7.
BMJ Paediatr Open ; 7(1)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37385734

RESUMO

BACKGROUND: Since most infants are usually discharged before age 48-72 hours, peak bilirubin levels will almost always occur after discharge. Parents may be the first to observe the onset of jaundice after discharge, but visual assessment is unreliable. The jaundice colour card (JCard) is a low-cost icterometer designed for the assessment of neonatal jaundice. The objective of this study was to evaluate parental use of JCard to detect jaundice in neonates. METHODS: We conducted a multicentre, prospective, observational cohort study in nine sites across China. A total of 1161 newborns ≥35 weeks of gestation were enrolled in the study. Measurements of total serum bilirubin (TSB) levels were based on clinical indications. The JCard measurements by parents and paediatricians were compared with the TSB. RESULTS: JCard values of parents and paediatricians were correlated with TSB (r=0.754 and 0.788, respectively). The parents' and paediatricians' JCard values 9 had sensitivities of 95.2% vs 97.6% and specificities of 84.5% vs 71.7% for identifying neonates with TSB ≥153.9 µmol/L. The parents' and paediatricians' JCard values 15 had sensitivities of 79.9% vs 89.0% and specificities of 66.7% vs 64.9% for identifying neonates with TSB ≥256.5 µmol/L. Areas under the receiver operating characteristic curves of parents for identifying TSB ≥119.7, ≥153.9, ≥205.2, and ≥256.5 µmol/L were 0.967, 0.960, 0.915, and 0.813, respectively, and those of paediatricians were 0.966, 0.961, 0.926 and 0.840, respectively. The intraclass correlation coefficient was 0.933 between parents and paediatricians. CONCLUSION: The JCard can be used to classify different levels of bilirubin, but it is less accurate with high bilirubin levels. The JCard diagnostic performance of parents was slightly lower than that of paediatricians.


Assuntos
Icterícia Neonatal , Idoso , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Bilirrubina , Icterícia Neonatal/diagnóstico , Pais , Estudos Prospectivos
8.
Mater Today Bio ; 20: 100661, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37229211

RESUMO

Matrix stiffness plays an important role in determining cell differentiation. The expression of cell differentiation-associated genes can be regulated by chromatin remodeling-mediated DNA accessibility. However, the effect of matrix stiffness on DNA accessibility and its significance for cell differentiation have not been investigated. In this study, gelatin methacryloyl (GelMA) hydrogels with different degrees of substitution were used to simulate soft, medium, and stiff matrices, and it was found that a stiff matrix promoted osteogenic differentiation of MC3T3-E1 cells by activating the Wnt pathway. In the soft matrix, the acetylation level of histones in cells was decreased, and chromatin condensed into a closed conformation, affecting the activation of ß-catenin target genes (Axin2, c-Myc). Histone deacetylase inhibitor (TSA) was used to decondense chromatin. However, there was no significant increase in the expression of ß-catenin target genes and the osteogenic protein Runx2. Further studies revealed that ß-catenin was restricted to the cytoplasm due to the downregulation of lamin A/C in the soft matrix. Overexpression of lamin A/C and concomitant treatment of cells with TSA successfully activated ß-catenin/Wnt signaling in cells in the soft matrix. The results of this innovative study revealed that matrix stiffness regulates cell osteogenic differentiation through multiple pathways, which involve complex interactions between transcription factors, epigenetic modifications of histones, and the nucleoskeleton. This trio is critical for the future design of bionic extracellular matrix biomaterials.

9.
Adv Healthc Mater ; 12(15): e2203106, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36906927

RESUMO

The mitochondrial permeability transition (mPT) directly affects mitochondrial function in macrophages. Under inflammatory conditions, mitochondrial calcium ion (mitoCa2+ ) overload triggers the persistent opening of mPT pores (mPTPs), further aggravating Ca2+ overload and increasing reactive oxygen species (ROS) to form an adverse cycle. However, there are currently no effective drugs targeting mPTPs to confine or unload excess Ca2+ . It is novelly demonstrated that the initiation of periodontitis and the activation of proinflammatory macrophages depend on the persistent overopening of mPTPs, which is mainly triggered by mitoCa2+ overload and facilitates further mitochondrial ROS leakage into the cytoplasm. To solve the above problems, mitochondrial-targeted "nanogluttons" with PEG-TPP conjugated to the surface of PAMAM and BAPTA-AM encapsulated in the core are designed. These nanogluttons can efficiently "glut" Ca2+ around and inside mitochondria to effectively control the sustained opening of mPTPs. As a result, the nanogluttons significantly inhibit the inflammatory activation of macrophages. Further studies also unexpectedly reveal that the alleviation of local periodontal inflammation in mice is accompanied by diminished osteoclast activity and reduced bone loss. This provides a promising strategy for mitochondria-targeted intervention in inflammatory bone loss in periodontitis and can be extended to treat other chronic inflammatory diseases associated with mitoCa2+ overload.


Assuntos
Cálcio , Periodontite , Camundongos , Animais , Espécies Reativas de Oxigênio , Proteínas de Transporte da Membrana Mitocondrial/fisiologia , Mitocôndrias , Íons , Periodontite/tratamento farmacológico
10.
Front Bioeng Biotechnol ; 11: 1113367, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761293

RESUMO

Purpose: In order to overcome the problem that conventional pharmacological treatments of periodontitis cannot effectively synergizing antimicrobial and immunomodulation, inspired by the critical role of toll-like receptor 4 (TLR4) in bacterial recognition and immune activation, we demonstrated a combined antibacterial-immunoregulatory strategy based on biomimetic nanoparticles. Methods: Functioned cell membranes and silk fibroin nanoparticles (SNs) loaded with minocycline hydrochloride (Mino) were used to prepare a biomimetic nanoparticle (MSNCs). SNs and MSNCs were characterized by Scanning Electron Microscope, size, zeta potential, dispersion index. At the same time, SNs were characterized by cell counting kit-8 and real-time Polymerase Chain Reaction (RT-PCR). TLR4-expressing cell membranes were characterized by RT-PCR and western blot (WB). Cell membrane coating was characterized by Transmission Electron Microscope (TEM), the Bradford staining and WB. Then, Laser confocal, flow cytometry and agar plate coating were evaluated in vitro with antibacterial effects, RT-PCR was simultaneously evaluated with immunoregulatory effects. Finally, Anti-inflammatory treatment of MSNCs was evaluated in a ligature-induced periodontitis (LIP) mouse model. Results: Successfully prepared cell membranes overexpressing TLR4 and constructed MSNCs. In vitro studies had shown that MSNCs effectively targeted bacteria via TLR4 and acted as molecular decoys to competitively neutralize lipopolysaccharide (LPS) in the microenvironment as well as inhibit inflammatory activation of macrophages. In vivo, MSNCs effectively attenuated periodontal tissue inflammation and alveolar bone loss in a LIP mouse model. Conclusion: MSNCs have good targeted antibacterial and immunoregulatory effects, and provide a new and effective strategy for the treatment of periodontitis and have good potential for application in various types of pathogenic bacterial infections.

11.
Telemed J E Health ; 29(8): 1211-1223, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36602780

RESUMO

Background and Objectives: Based on practical services of the Henan Province Telemedicine Center (HTCC), the purpose of this study is to investigate the design, construction, implementation, and application effect of a specific telemedicine system in response to the coronavirus disease 2019 (COVID-19). Methods: Data on COVID-19 cases from December 31, 2019, through October 17, 2022, were collected from official websites. Data and information of telemedicine services related to COVID-19 in HTCC were collected and analyzed, and relevant graphical representations were plotted. Results: All the 147 COVID-19 designated hospitals in the Henan Province were covered by the specific telemedicine system. The cities near to the Hubei Province in the south of Henan tended to be with more COVID-19 cases, where more COVID-19-related telemedicine services were conducted. For the telemedicine system, function modules, including real-time monitoring, command and dispatch, intractable cases transfer, remote guidance, and data sharing, were designed and realized to deal with COVID-19. Through the system, telemedicine services involved COVID-19 such as epidemic surveillance, emergency rescue, case discussion, diagnosis and treatment, remote ward-round, and distance education were performed. During the period between February 2 and March 3, 2020, 646 COVID-19 patients were served by the telemedicine system, with an improvement rate of 73.2%. Conclusions: Telemedicine can improve the diagnosis and treatment of COVID-19 patients, which play a helpful role in curbing the COVID-19 epidemic. Given the current global COVID-19 pandemic and the potential re-emerge of novel zoonotic pathogens in the future, the use of telemedicine would be imperative to fight against the pandemic.


Assuntos
COVID-19 , Telemedicina , Humanos , COVID-19/epidemiologia , COVID-19/terapia , SARS-CoV-2 , Pandemias , China/epidemiologia
12.
Zhongguo Zhen Jiu ; 42(11): 1211-5, 2022 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-36397216

RESUMO

OBJECTIVE: To observe the effect of Huayu Tongluo (resolving stasis and promoting collateral circulation) moxibustion combined with intradermal needling on depressive symptoms, quality of life and cognitive impairment in patients with mild to moderate depression after cerebral infarction on the basis of western medicine treatment. METHODS: Fifty patients with mild to moderate depression after cerebral infarction were randomly divided into an acupuncture combined with western medication group (group A, 25 cases) and a western medication group (group B, 25 cases). In the group B, paroxetine hydrochloride tablets were taken orally, 20 mg after breakfast, once a day, and the dose could be adjusted to the maximum 40 mg/d according to the patients' condition, for 4 weeks totally. On the basis of the treatment in the group B, the group A was treated with Huayu Tongluo moxibustion, namely aconite cake-separated moxibustion at Baihui (GV 20) and suspended moxibustion at Dazhui (GV 14) and Shenting (GV 24), combined with intradermal needling at Shenmen (HT 7), Jianshi (PC 5), Zusanli (ST 36), etc. Huayu Tongluo moxibustion was performed 6 times a week, and intradermal needling was performed 3 times a week,for 4 weeks totally. In the two groups, the scores of Hamilton depression scale (HAMD), stroke specific quality of life scale (SS-QOL) and mini mental state examination (MMSE) were observed before and after treatment, and the clinical efficacy and safety were compared. RESULTS: After treatment, the HAMD score in the each group was decreased compared with that before treatment (P<0.05), and that in the group A was lower than the group B (P<0.05); after treatment, the SS-QOL score in the group A and MMSE score in the two groups were increased compared with those before treatment (P<0.05), and the SS-QOL score in the group A was higher than the group B (P<0.05). The total effective rate was 88.0% (22/25) in the group A, which was higher than 60.0% (15/25) in the group B (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (4.0% [1/25] vs 16.0%[4/25], P>0.05). CONCLUSION: On the basis of the treatment of western medication paroxetine hydrochloride tablets, Huayu Tongluo moxibustion combined with intradermal needling therapy can effectively improve the depressive symptoms, quality of life and cognitive impairment of patients with mild to moderate depression after cerebral infarction.


Assuntos
Moxibustão , Humanos , Qualidade de Vida , Paroxetina , Depressão/etiologia , Depressão/terapia , Infarto Cerebral/complicações , Infarto Cerebral/terapia
13.
J Chem Phys ; 157(8): 084106, 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36049989

RESUMO

This paper combines the valence bond block diabatization approach with the idea of orbital breathing. With highly compact wave functions, the breathing orbital valence bond (BOVB) method is applied to investigate several atomic and molecular properties, including the electron affinity of F, the adiabatic and diabatic potential energy curves and the dipole moment curves of the two lowest-lying 1Σ+ states, the electronic coupling curve and the crossing distance of the two diabatic states, and the spectroscopic constants of the ground states for LiF. The configuration selection scheme proposed in this work is quite general, requiring only the selection of several de-excitation and excitation orbitals in a sense like the restricted active space self-consistent field method. Practically, this is also the first time that BOVB results are extrapolated to complete basis set limit. Armed with the chemical intuition provided by valence bond theory, the classic but challenging covalent-ionic interaction in the title molecule is not only conceptually interpreted but also accurately computed.

14.
Water Res ; 219: 118537, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35526431

RESUMO

Global impoundment of river systems represents a major anthropogenic forcing to carbon cycling in reservoirs with seasonal thermal stratification. Currently, a quantitative and mechanistic understanding of how hypolimnetic deoxygenation in stratified reservoirs alters dissolved organic matter (DOM) cycling and lateral transport along the river continuum remains unresolved. Herein, we used optical and high-resolution mass spectrometric analyses to track seasonal and spatial compositional changes of DOM from a large, subtropical impounded river in southeast China. Aliphatic compounds were contributed by algal blooms to epilimnetic DOM during the spring/summer and by baseflow to the overall DOM pool during low-discharge periods. Deoxygenation-driven hypolimnetic mineralization enhanced in situ production of bio-refractory molecules and humic-like fluorescent DOM (FDOMH) by utilizing bio-labile DOM and settling biogenic particles during periods of stratification. Production efficiency of hypolimnetic FDOMH was 159-444% higher than that of the global dark ocean, and was strongly regulated by temperature and possibly substrate supply. The in situ production rate of hypolimnetic FDOMH was four to five orders-of-magnitude higher than the dark ocean, with much faster turnover rates in dark inland waters versus the dark ocean. Collectively, these findings indicate that the hypolimnion is a hotspot for microbial carbon transformations, and hence an important source and pool of refractory DOM in aquatic systems. The lateral FDOMH flux increased 10.8-32.1% due to hypolimnetic reservoir release during periods of stratification, highlighting the importance of incorporating hypolimnetic carbon transformations into models for carbon cycling of inland waters and the land-sea interface.


Assuntos
Matéria Orgânica Dissolvida , Carbono , Rios , Estações do Ano
15.
Biosens Bioelectron ; 207: 114112, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429796

RESUMO

The selective and sensitive detection of cancerous exosomes in serum is critical for early disease diagnosis and improved prognosis. Previous exosome-related research has been limited by a lack of well-understanding in exosomes as well as the challenging background interference of body fluid. Molecularly imprinted polymers (MIPs) and nucleic acid aptamers can be regarded as the two alternatives to antibodies. When using imprinted polymer technology, comprehensive and precise information about the target constituents is not required. In this study, a novel kind of dual selective fluorescent nanosensor for the poorly characterized exosomes was constructed by integrating magnetic MIP selective exosome capture sandwiched with an aptamer/graphene oxide fluorescence resonance energy transfer system (FRET) based selective 'turn-on' exosome labeling heterogeneously. The overall strategy performance was successively evaluated using lysozyme and exosomes as targets. Good linearity and high sensitivity achieved were demonstrated. The LOD of exosomal detection in serum was 2.43 × 106 particles/mL, lower than other immunology based detection methods. The discrimination between serum from breast cancer patients and healthy people was also primarily studied. In conclusion, the developed sensor with outstanding selectivity, high detection sensitivity, simplicity, low cost, and wide applicability for known or unknown targets present significant potential in challenging clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Exossomos , Impressão Molecular , Técnicas Biossensoriais/métodos , Transferência Ressonante de Energia de Fluorescência/métodos , Grafite , Humanos , Fenômenos Magnéticos , Oligonucleotídeos , Polímeros
16.
Bioact Mater ; 18: 254-266, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35387157

RESUMO

Precise and controlled drug delivery to treat periodontitis in patients with diabetes remains a significant clinical challenge. Nanoparticle-based drug delivery systems offer a potential therapeutic strategy; however, the low loading efficiency, non-responsiveness, and single effect of conventional nanoparticles hinder their clinical application. In this study, we designed a novel self-assembled, dual responsive, and dual drug-loading nanocarrier system, which comprised two parts: the hydrophobic lipid core formed by 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly (ethylene glycol) (DSPE-PEG) loaded with alpha-lipoic acid (ALA); and a hydrophilic shell comprising a poly (amidoamine) dendrimer (PAMAM) that electrostatically adsorbed minocycline hydrochloride (Mino). This unique design allows the controlled release of antioxidant/ALA under lipase stimulation from periodontal pathogens and antimicrobial/Mino under the low pH of the inflammatory microenvironment. In vivo and in vitro studies confirmed that this dual nanocarrier could inhibit the formation of subgingival microbial colonies while promoting osteogenic differentiation of cells under diabetic pathological conditions, and ameliorated periodontal bone resorption. This effective and versatile drug-delivery strategy has good potential applications to inhibit diabetes-associated periodontal bone loss.

17.
Stem Cell Res Ther ; 13(1): 26, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35073961

RESUMO

BACKGROUND: Cartilage defects pose a significant burden on medical treatment, leading to an urgent need to develop regenerative medicine approaches for cartilage repair, such as stem cell therapy. However, the direct injection of stem cells can result in insufficient delivery or inaccurate differentiation. Hence, it is necessary to choose appropriate stem cell delivery scaffolds with high biocompatibility, injectability and chondral differentiation induction ability for cartilage regeneration. METHODS: In this study, the photocrosslinked gelatin methacrylate (GelMA) hydrogel with high cell affinity and plasticity was selected and strengthened by incorporating methacrylic anhydride-modified poly(amidoamine) (PAMAM-MA) to fabricate an adipose-derived stromal/stem cells (ASCs) delivery scaffold for cartilage repair. The physiochemical properties of the GelMA/PAMAM-MA hydrogel, including the internal structure, stability and mechanical properties, were tested. Then, ASCs were encapsulated into the hydrogels to determine the in vitro and in vivo chondrogenic differentiation induction abilities of the GelMA/PAMAM-MA hydrogel. RESULTS: Compared with the GelMA hydrogel, the GelMA/PAMAM-MA hydrogel exhibited more uniform structure, stability and mechanical properties. Moreover, on the basis of good biocompatibility, the hybrid hydrogel was proven to exert a sufficient ability to promote cartilage regeneration by in vitro three-dimensional (3D) culture of rASCs and in vivo articular cartilage defect repair. CONCLUSIONS: The injectable photocrosslinked GelMA/PAMAM-MA hydrogel was proven to be a capable stem cell carrier for cartilage repair and provides new insight into the design strategy of stem cell delivery scaffolds.


Assuntos
Cartilagem Articular , Dendrímeros , Gelatina/química , Hidrogéis/química , Metacrilatos/química , Células-Tronco , Engenharia Tecidual/métodos
18.
Food Chem ; 373(Pt B): 131501, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-34763932

RESUMO

Phytosterols have gained much attention due to their outstanding cholesterol-reducing effect, while the insolubility in water limits their application. The aim of this study was to synthesize a novel hydrophilic phytosteryl derivatives-phytosteryl succinyl sucrose esters (PSSEs) and investigated their water solubility and emulsifying properties. PSSEs were synthesized by esterifying phytosterol hemisuccinates with sucrose through a mild chemical reaction. PSSEs were characterized by fourier transform infrared spectroscopy, mass spectroscopy, and nuclear magnetic resonance spectroscopy. The yield of PSSEs exceeded 84% in N,N-dimethylformamide for 36 h of reaction under the selected conditions: 100 mmol/L phytosteryl hemisuccinates, 150 mmol/L sucrose, 110 mmol/L 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochlide, 10 mmol/L 4-dimethylaminopyridine and 10 mmol/L p-toluenesulfonic acid. The water insolubility of phytosterols was overcome and the water solubility of PSSEs achieved 2.13 mg/mL. The emulsifying activity of PSSEs was 2.5 times that of phytosterols, reaching 0.95 mg/mL. PSSEs with better water solubility and emulsification properties could facilitate the widespread use of phytosterols in foods.


Assuntos
Ésteres , Fitosteróis , Solubilidade , Sacarose , Água
19.
J Chem Theory Comput ; 17(11): 6861-6875, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34605634

RESUMO

A novel adiabatic-to-diabatic (ATD) transformation strategy, namely, the extended Mulliken-Hush (XMH) method, is proposed to evaluate diabatic properties including electronic couplings, potential energy surfaces, and their crossings. The XMH method is developed by adopting our recently proposed ATD transformation formula of a general vectorial physical observable, in which a useful ATD transformation is further determined by using an auxiliary dipole between localized frontier orbitals as a simple approximation of the diabatic transition dipole. The XMH method is simple and practical that provides a flexible way to construct diabatic states. To some extent, it can be regarded as an extension of the generalized Mulliken-Hush (GMH) method since the latter takes a stronger approximation, in which the diabatic transition dipole is assumed to be vanishing. Test calculations on the HeH2+ system show that the electronic couplings predicted by the XMH method are closer to the ones calculated by the valence bond block-diagonalization approach than the GMH ones since the XMH method takes into account both the magnitude and direction of the diabatic transition dipole, which is consistent with the properties of this molecule. In the study of electron transfer in the two kinds of donor-bridge-acceptor systems, the XMH method maintains the simplicity of the GMH method and gives reasonable results even when the latter fails, wherein the diabatic transition dipole is nearly perpendicular to the difference of the initial and final adiabatic dipoles. More importantly, the XMH method can be easily combined with high-level electronic structure methods, in which the properties of the ground and excited states may be more accurately calculated, and hence, one may expect that further development of the XMH method would result in a general computational model for studying electron transfer reactions.

20.
J Mater Chem B ; 9(12): 2831-2844, 2021 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-33704322

RESUMO

Bone targeting is one of the most potentially valuable therapeutic methods for medically treating bone diseases, such as osteoarthritis, osteoporosis, nonunion bone defects, bone cancer, and myeloma-related bone disease, but its efficacy remains a challenge due to unfavorable bone biodistribution, off-target effects, and the lack of cell specificity. To address these problems, we synthesized a new dual-targeting nanocarrier for delivery to bone by covalently modifying the G4.0 PAMAM dendrimer with the C11 peptide and the CH6 aptamer (CH6-PAMAM-C11). The molecular structure was confirmed using 1H-NMR and FT-IR spectroscopy. CLSM results showed that the novel nanocarrier could successfully accumulate in the targeted cells, mineralized areas and tissues. DLS and TEM demonstrated that CH6-PAMAM-C11 was approximately 40-50 nm in diameter. In vitro targeting experiments confirmed that the C11 ligand had a high affinity for HAP, while the CH6 aptamer had a high affinity for osteoblasts. The in vivo biodistribution analysis showed that CH6-PAMAM-C11 could rapidly accumulate in bone within 4 h and 12 h and then deliver drugs to sites of osteoblast activity. The components of CH6-PAMAM-C11 were well excreted via the kidneys. The accumulation of many more CH6-PAMAM-C11 dual-targeting nanocarriers than single-targeting nanocarriers was observed in the periosteal layer of the rat skull, along with aggregation at sites of osteoblast activity. All of these results indicate that CH6-PAMAM-C11 may be a promising nanocarrier for the delivery of drugs to bone, particularly for the treatment of osteoporosis, and our research strategy may serve as a reference for research in targeted drug, small molecule drug and nucleic acid delivery.


Assuntos
Aptâmeros de Nucleotídeos/química , Osso e Ossos/efeitos dos fármacos , Dendrímeros/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Oligopeptídeos/química , Vitamina D/farmacologia , Animais , Células Cultivadas , Portadores de Fármacos/química , Camundongos , Osteoblastos/efeitos dos fármacos , Ratos , Vitamina D/química
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