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1.
Biomaterials ; 311: 122659, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38861831

RESUMO

Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H2Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H2Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H2Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H2Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.

2.
J Agric Food Chem ; 72(25): 14337-14348, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38867141

RESUMO

Thymol has efficient bactericidal activity against a variety of pathogenic bacteria, but the bactericidal mechanism against Vibrio parahemolyticus (V. parahemolyticus) has rarely been reported. In the current study, we investigated the bactericidal mechanism of thymol against V. parahemolyticus. The Results revealed that 150 µg/mL of thymol had 99.9% bactericidal activity on V. parahemolyticus. Intracellular bursts of reactive oxygen species (ROS), Fe2+accumulation, lipid peroxidation, and DNA breakage were checked by cell staining. The exogenous addition of H2O2 and catalase promoted and alleviated thymol-induced cell death to a certain extent, respectively, and the addition of the ferroptosis inhibitor Liproxstatin-1 also alleviated thymol-induced cell death, confirming that thymol induced Fenton-reaction-dependent ferroptosis in V. parahemolyticus. Proteomic analysis revealed that relevant proteins involved in ROS production, lipid peroxidation accumulation, and DNA repair were significantly upregulated after thymol treatment. Molecular docking revealed two potential binding sites (amino acids 46H and 42F) between thymol and ferritin, and thymol could promote the release of Fe2+ from ferritin proteins through in vitro interactions analyzed. Therefore, we hypothesized that ferritin as a potential target may mediate thymol-induced ferroptosis in V. parahemolyticus. This study provides new ideas for the development of natural inhibitors for controlling V. parahemolyticus in aquatic products.


Assuntos
Antibacterianos , Ferroptose , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio , Timol , Vibrio parahaemolyticus , Ferroptose/efeitos dos fármacos , Timol/farmacologia , Timol/química , Espécies Reativas de Oxigênio/metabolismo , Vibrio parahaemolyticus/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Ferro/metabolismo , Simulação de Acoplamento Molecular , Ferritinas/genética , Ferritinas/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética
3.
J Med Chem ; 67(11): 9028-9053, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38787534

RESUMO

This work identified a class of cyanomethylquinolones (CQs) and their carboxyl analogues as potential multitargeting antibacterial candidates. Most of the prepared compounds showed high antibacterial activities against most of the tested bacteria, exhibiting lower MIC values (0.125-2 µg/mL) than those of clinical norfloxacin, ciprofloxacin, and clinafloxacin. The low hemolysis, drug resistance, and cytotoxicity, as well as good predictive pharmacokinetics of active CQs and carboxyl analogues revealed their development potential. Furthermore, they could eradicate the established biofilm, facilitating bacterial exposure to these antibacterial candidates. These active compounds could induce bacterial death through multitargeting effects, including intercalating into DNA, up-regulating reactive oxygen species, damaging membranes directly, and impeding metabolism. Moreover, the highly active cyclopropyl CQ 15 exhibited more effective in vivo anti-MRSA potency than ciprofloxacin. These findings highlight the potential of CQs and their carboxyl analogues as multitargeting broad-spectrum antibacterial candidates for treating intractable bacterial infections.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Quinolonas , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Quinolonas/farmacologia , Quinolonas/química , Quinolonas/síntese química , Humanos , Relação Estrutura-Atividade , Biofilmes/efeitos dos fármacos , Camundongos , Hemólise/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Ciprofloxacina/análogos & derivados , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
4.
Int J Oral Sci ; 16(1): 32, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627388

RESUMO

Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.


Assuntos
Má Oclusão , Humanos , Criança , Consenso , Má Oclusão/epidemiologia , Assistência Odontológica , China
5.
Biosens Bioelectron ; 255: 116235, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38579623

RESUMO

Multiplexed immunodetection, which achieves qualitative and quantitative outcomes for multiple targets in a single-run process, provides more sufficient results to guarantee food safety. Especially, lateral flow immunoassay (LFIA), with the ability to offer multiple test lines for analytes and one control line for verification, is a forceful candidate in multiplexed immunodetection. Nevertheless, given that single-signal mode is incredibly vulnerable to interference, further efforts should be engrossed on the combination of multiplexed immunodetection and multiple signals. Photothermal signal has sparked significant excitement in designing immunosensors. In this work, by optimizing and comparing the amount of gold, CuS@Au heterojunctions (CuS@Au HJ) were synthesized. The dual-plasmonic metal-semiconductor hybrid heterojunction exhibits a synergistic photothermal performance by increasing light absorption and encouraging interfacial electron transfer. Meanwhile, the colorimetric property is synergistic enhanced, which is conducive to reduce the consumption of antibodies and then improve assay sensitivity. Therefore, CuS@Au HJ are suitable to be constructed in a dual signal and multiplexed LFIA (DSM-LFIA). T-2 toxin and deoxynivalenol (DON) were used as model targets for the simulated multiplex immunoassay. In contrast to colloidal gold-based immunoassay, the built-in sensor has increased sensitivity by ≈ 4.42 times (colorimetric mode) and ≈17.79 times (photothermal mode) for DON detection and by ≈ 1.75 times (colorimetric mode) and ≈13.09 times (photothermal mode) for T-2 detection. As a proof-of-concept application, this work provides a reference to the design of DSM-LFIA for food safety detection.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Colorimetria , Imunoensaio , Metais
6.
J Agric Food Chem ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38624165

RESUMO

Immunochromatography (ICA) remains untapped toward enhanced sensitivity and applicability for fulfilling the nuts and bolts of on-site food safety surveillance. Herein, we report a fortified dual-spectral overlap with enhanced colorimetric/fluorescence dual-response ICA for on-site bimodal-type gentamicin (Gen) monitoring by employing polydopamine (PDA)-coated AuNPs (APDA) simultaneously serving as a colorimetric reporter and a fluorescence quencher. Availing of the enhanced colorimetric response that originated from the PDA layer, the resultant APDA exhibits less required antibody and immunoprobes in a single immunoassay, which facilitates improved antibody utilization efficiency and immuno-recognition in APDA-ICA. Further integrated with the advantageous features of fortified excitation and emission dual-spectral overlap for the Arg/ATT-AuNCs, this APDA-ICA with a "turn on/off" pattern achieves the visual limits of detection of 1.0 and 0.5 ng mL-1 for colorimetric and fluorescence patterns (25- and 50-fold lower than standard AuNPs-ICA). Moreover, the excellent self-calibration and satisfactory recovery of 79.03-118.04% were shown in the on-site visual colorimetric-fluorescence analysis for Gen in real environmental media (including real river water, an urban aquaculture water body, an aquatic product, and an animal byproduct). This work provides the feasibility of exploiting fortified dual-spectral overlap with an enhanced colorimetric/fluorescence dual response for safeguarding food safety and public health.

7.
Se Pu ; 42(3): 304-308, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38503708

RESUMO

To solve the problems of the lack of property research in organic synthesis experiments and the relative independence of instrumental analytical methods in experiments, we designed a comprehensive undergraduate experiment based on mechanofluorochromic materials. In this project, 4-[bis(4-methylphenyl)amino] benzaldehyde was synthesized via the Vilsmeier-Haack reaction using 4,4'-dimethyltriphenylamine as the raw material. The product was then characterized by mass spectrometry, infrared absorption spectroscopy, and nuclear magnetic resonance spectroscopy. The solvatofluorochromism and mechanofluorochromism of the target material were studied using ultraviolet-visible absorption spectroscopy, fluorescence spectroscopy, etc. Furthermore, the mechanism of mechanofluorochromism was determined using powder X-ray diffraction. Organic synthesis and a series of instrumental analytical methods were combined to form an integrated experiment. The experiment is interesting, scientific, and comprehensive for undergraduates as a creative exercise; moreover, it can inspire their interest in chemical research, cultivate a variety of experimental operation abilities, improve creative-thinking skills, and encourage the development of effective solutions to existing problems in chemical experiments.

8.
Lab Chip ; 24(8): 2272-2279, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38504660

RESUMO

A highly sensitive lateral flow immunoassay (LFIA) is developed for the enzyme-catalyzed and double-reading determination of clenbuterol (CLE), in which a new type of probe was adopted through the direct electrostatic adsorption of ultra-small copper-gold bimetallic enzyme mimics (USCGs) and monoclonal antibodies. In the assay, based on the peroxidase activity of USCG, the chromogenic substrate TMB-H2O2 was introduced to trigger its color development, and the results were compared with those before catalysis. The detection sensitivity after catalysis is 0.03 ng mL-1 under optimal circumstances, which is 6-fold better than that of the traditional Au NPs-based LFIA and 2-fold greater than that before catalysis. This approach was successfully applied to the detection of CLE in milk, pork and mutton samples with an optimum assay time of 7 min and best catalytic time of 80 s, after which satisfactory recoveries of 98.53-117.79% were obtained. Cu-Au nanoparticles as a signal tag and the use of their nanozyme properties are the first applications in the field of LFIA. This work can be a promising exhibition for the application of a cheaper substitute for HRP, ultra-small bimetallic enzyme mimics, in LFIAs.


Assuntos
Clembuterol , Nanopartículas Metálicas , Limite de Detecção , Cobre , Ouro/química , Peróxido de Hidrogênio , Nanopartículas Metálicas/química , Catálise , Imunoensaio/métodos
9.
ACS Appl Mater Interfaces ; 16(12): 15394-15404, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38489480

RESUMO

External stimuli-responsive DNA hydrogels present interesting platforms for drug loading and triggered release. Typically, drug molecules are encapsulated within three-dimensionally hybridized DNA networks. However, the utilization of drug molecules as cofactors to facilitate the directed assembly of DNA strands into hydrogel frameworks and their subsequent controlled release remains to be explored. Herein, we introduce the guided assembly of oligo-adenine (A-strand) into an acidic pH-responsive DNA hydrogel using an anticancer drug, coralyne (COR), as a low-molecular-weight cofactor. At pH 7, COR orchestrates the assembly of A-strand into an antiparallel duplex configuration cross-linked by A-COR-A units at a stoichiometric ratio of one COR cofactor per four adenine bases, resulting in a DNA hydrogel characterized by A-COR-A duplex bridges. At pH 4-5, the instability of A-COR-A units results in the disintegration of the duplex into its constituent components, leading to the release of COR and simultaneous dissociation of the DNA hydrogel matrix. This study introduces a method by which drug molecules, exemplified here by COR, facilitate the direct formation of a supramolecular cofactor-DNA complex, subsequently leading to the creation of a stimuli-responsive DNA hydrogel. This approach may inspire future investigations into DNA hydrogels tailored for controlled drug encapsulation and release applications.


Assuntos
Adenina , Alcaloides de Berberina , Hidrogéis , Hidrogéis/química , DNA/química , Concentração de Íons de Hidrogênio
10.
Anal Chem ; 96(12): 5046-5055, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38488055

RESUMO

Bimodal-type multiplexed immunoassays with complementary mode-based correlation analysis are gaining increasing attention for enhancing the practicability of the lateral flow immunoassay (LFIA). Nonetheless, the restriction in visually indistinguishable multitargets induced by a single fluorescent color and difficulty in single acceptor ineffectual fluorescence quenching due to the various spectra of multiple different donors impede the further execution of colorimetric-fluorescence bimodal-type multiplexed LFIAs. Herein, the precise spectral overlap-based donor-acceptor pair construction strategy is proposed by regulating the size of the nanocore, coating it with an appropriate nanoshell, and selecting a suitable fluorescence donor with distinct colors. By in situ coating Prussian blue nanoparticles (PBNPs) on AuNPs with a tunable size and absorption spectrum, the resultant APNPs demonstrate efficient fluorescence quenching ability, higher colloidal stability, remarkable colorimetric intensity, and an enhanced antibody coupling efficiency, all of which facilitate highly sensitive bimodal-type LFIA analysis. Following integration with competitive-type immunoreaction, this precise spectral overlap-supported spatial separation traffic light-typed colorimetric-fluorescence dual-response assay (coined as the STCFD assay) with the limits of detection of 0.013 and 0.152 ng mL-1 for ractopamine and clenbuterol, respectively, was proposed. This work illustrates the superiority of the rational design of a precise spectral overlap-based donor-acceptor pair, hinting at the enormous potential of the STCFD assay in the point-of-care field.


Assuntos
Clembuterol , Nanopartículas Metálicas , Ouro , Imunoensaio , Fenômenos Químicos , Limite de Detecção
11.
World J Clin Cases ; 12(4): 688-699, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38322692

RESUMO

Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored. However, it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system., and has accordingly been a focus of extensive clinical research. As a traditional Chinese medicinal formulation, Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases. Its main constituents include Citrus aurantium, Magnolia officinalis, rhubarb, and Qiangwu, which are primarily used to regulate qi. In the treatment of neurological diseases, the therapeutic effects of the Sanhua Decoction are mediated via different pathways, including antioxidant, anti-inflammatory, and neurotransmitter regulatory pathways, as well as through the protection of nerve cells and a reduction in cerebral edema. Among the studies conducted to date, many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects. In addition, as a natural treatment, the Sanhua Decoction has received widespread attention, given that it is safer and more effective than traditional Western medicines. Consequently, research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance. In this paper, we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction. We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion, and provide a scientific basis for its application in clinical practice.

12.
J Ultrasound Med ; 43(6): 1013-1024, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38323467

RESUMO

OBJECTIVES: The coronal plane is the unique display mode of automated breast (AB) ultrasound (US), which has valuable features of showing the entire breast anatomy and providing additional diagnostic value for breast lesions. However, whether adding the coronal plane could improve the diagnostic performance in screening breast cancer remains uncertain. This study aimed to evaluate the value of adding the coronal plane in interpretation for AB US screening. METHODS: In this retrospective study, AB US images from 644 women (396 in the no-finding group, 143 with benign lesions, and 105 with malignant lesions) aged 40-70 years were collected between January 2016 and October 2020. Four novice radiologists (with 1-5 years of experience with breast US) and four experienced radiologists (with >5 years of experience with breast US) were assigned to read all AB US images in the transverse plane plus coronal plane (T + C planes) and transverse plane (T plane) alone in separate reading sessions. Diagnostic performance, lesion conspicuity, and reading time were compared using analysis of variance. RESULTS: The mean reading time of all radiologists was significantly shorter in the T + C planes reading mode than in the T plane alone (115 ± 32 vs 128 ± 31 s, respectively; P < .05), and cancers had a higher conspicuity (odds ratio, 1.76; 95% confidence interval [CI], 1.00-3.08; P = .04). No significant differences were noted in the two reading modes (T + C planes vs T plane) in the sensitivity (82% [95% CI, 74-89%] vs 81% [95% CI, 74-88%], respectively; P = .68) and specificity (68% [95% CI, 62-75%] vs 70% [95% CI, 64-75%], respectively; P = .39) when Breast Imaging-Reporting and Data System (BI-RADS) 3 was set as the threshold. There were also no significant differences in the two reading modes (T + C planes vs T plane) in the sensitivity (70% [95% CI, 64-76%] vs 69% [95% CI, 63-75%], respectively; P = .39) and specificity (91% [95% CI, 87-96%] vs 91% [95% CI, 88-95%], respectively; P = .90) when BI-RADS 4 was set as the threshold. In addition, the mean areas under the receiver operating characteristic curves of all radiologists in the two reading modes (T + C planes vs T plane) were not significantly different (0.84 [95% CI, 0.79-0.89] vs 0.83 [95% CI, 0.78-0.89], respectively; P = .61). CONCLUSIONS: Adding a coronal plane in the AB US screening setting saved the reading time and improved the conspicuity of breast cancers but not the diagnostic performance.


Assuntos
Neoplasias da Mama , Mama , Sensibilidade e Especificidade , Ultrassonografia Mamária , Humanos , Feminino , Pessoa de Meia-Idade , Ultrassonografia Mamária/métodos , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Idoso , Adulto , Mama/diagnóstico por imagem , Reprodutibilidade dos Testes
13.
J Lipid Res ; 65(3): 100513, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38295985

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease without specific Food and Drug Administration-approved drugs. Recent advances suggest that chromatin remodeling and epigenetic alteration contribute to the development of NAFLD. The functions of the corresponding molecular modulator in NAFLD, however, are still elusive. KDM1A, commonly known as lysine-specific histone demethylase 1, has been reported to increase glucose uptake in hepatocellular carcinoma. In addition, a recent study suggests that inhibition of KDM1A reduces lipid accumulation in primary brown adipocytes. We here investigated the role of KDM1A, one of the most important histone demethylases, in NAFLD. In this study, we observed a significant upregulation of KDM1A in NAFLD mice, monkeys, and humans compared to the control group. Based on these results, we further found that the KDM1A can exacerbate lipid accumulation and inflammation in hepatocytes and mice. Mechanistically, KDM1A exerted its effects by elevating chromatin accessibility, subsequently promoting the development of NAFLD. Furthermore, the mutation of KDM1A blunted its capability to promote the development of NAFLD. In summary, our study discovered that KDM1A exacerbates hepatic steatosis and inflammation in NAFLD via increasing chromatin accessibility, further indicating the importance of harnessing chromatin remodeling and epigenetic alteration in combating NAFLD. KDM1A might be considered as a potential therapeutic target in this regard.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Cromatina/genética , Histona Desmetilases/genética , Inflamação/genética , Lipídeos
14.
Mater Today Bio ; 24: 100933, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38283982

RESUMO

Injured articular cartilage is a leading cause for osteoarthritis. We recently discovered that endogenous stem/progenitor cells not only reside in the superficial zone of mouse articular cartilage, but also regenerated heterotopic bone and cartilage in vivo. However, whether critical-size osteochondral defects can be repaired by pure induced chemotatic cell homing of these endogenous stem/progenitor cells remains elusive. Here, we first found that cells in the superficial zone of articular cartilage surrounding surgically created 3 × 1 mm defects in explant culture of adult goat and rabbit knee joints migrated into defect-filled fibrin/hylaro1nate gel, and this migration was significantly more robust upon delivery of exogenous granulocyte-colony stimulating factor (G-CSF). Remarkably, G-CSF-recruited chondrogenic progenitor cells (CPCs) showed significantly stronger migration ability than donor-matched chondrocytes and osteoblasts. G-CSF-recruited CPCs robustly differentiated into chondrocytes, modestly into osteoblasts, and barely into adipocytes. In vivo, critical-size osteochondral defects were repaired by G-CSF-recruited endogenous cells postoperatively at 6 and 12 weeks in comparison to poor healing by gel-only group or defect-only group. ICRS and O'Driscoll scores of articular cartilage were significantly higher for both 6- and 12-week G-CSF samples than corresponding gel-only and defect-only groups. Thus, endogenous stem/progenitor cells may be activated by G-CSF, a Food and Drug Administration (FDA)-cleared bone-marrow stimulating factor, to repair osteochondral defects.

15.
Eur J Med Chem ; 265: 116107, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38171147

RESUMO

Unique benzopyridone cyanoacetates (BCs) as new type of promising broad-spectrum antibacterial candidates were discovered with large potential to combat the lethal multidrug-resistant bacterial infections. Many prepared BCs showed broad antibacterial spectrum with low MIC values against the tested strains. Some highly active BCs exhibited rapid sterilization capacity, low resistant trend and good predictive pharmacokinetic properties. Furthermore, the highly active sodium BCs (NaBCs) displayed low hemolysis and cytotoxicity, and especially octyl NaBC 5g also showed in vivo potent anti-infective potential and appreciable pharmacokinetic profiles. A series of preliminary mechanistic explorations indicated that these active BCs could effectively eliminate bacterial biofilm and destroy membrane integrity, thus resulting in the leakage of bacterial cytoplasm. Moreover, their unique structures might further bind to intracellular DNA, DNA gyrase and topoisomerase IV through various direct noncovalent interactions to hinder bacterial reproduction. Meanwhile, the active BCs also induced bacterial oxidative stress and metabolic disturbance, thereby accelerating bacterial apoptosis. These results provided a bright hope for benzopyridone cyanoacetates as potential novel multitargeting broad-spectrum antibacterial candidates to conquer drug resistance.


Assuntos
Antibacterianos , Inibidores da Topoisomerase II , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias , DNA Girase/metabolismo , DNA Topoisomerase IV , Testes de Sensibilidade Microbiana , Inibidores da Topoisomerase II/farmacologia , Piridonas/química , Piridonas/farmacologia , Nitrilas/química , Nitrilas/farmacologia
16.
Adv Mater ; 36(9): e2305277, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37526952

RESUMO

Nanomaterial-mediated ferroptosis has garnered considerable interest in the antibacterial field, as it invokes the disequilibrium of ion homeostasis and boosts lipid peroxidation in extra- and intracellular bacteria. However, current ferroptosis-associated antibacterial strategies indiscriminately pose damage to healthy cells, ultimately compromising their biocompatibility. To address this daunting issue, this work has designed a precise ferroptosis bio-heterojunction (F-bio-HJ) consisting of Fe2 O3 , Ti3 C2 -MXene, and glucose oxidase (GOx) to induce extra-intracellular bacteria-targeted ferroptosis for infected diabetic cutaneous regeneration. Fe2 O3 /Ti3 C2 -MXene@GOx (FMG) catalytically generates a considerable amount of ROS which assaults the membrane of extracellular bacteria, facilitating the permeation of synchronously generated Fe2+ /Fe3+ into bacteria under near-infrared (NIR) irradiation, causing planktonic bacterial death via ferroptosis, Fe2+ overload, and lipid peroxidation. Additionally, FMG facilitates intracellular bacterial ferroptosis by transporting Fe2+ into intracellular bacteria via inward ferroportin (FPN). With GOx consuming glucose, FMG creates hunger protection which helps macrophages escape cell ferroptosis by activating the adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) pathway. In vivo results authenticate that FMG boosts diabetic infectious cutaneous regeneration without triggering ferroptosis in normal cells. As envisaged, the proposed tactic provides a promising approach to combat intractable infections by precisely terminating extra-intracellular infection via steerable ferroptosis, thereby markedly elevating the biocompatibility of therapeutic ferroptosis-mediated strategies.


Assuntos
Diabetes Mellitus , Ferroptose , Nitritos , Elementos de Transição , Citoproteção , Fome , Antibacterianos/farmacologia , Glucose Oxidase
17.
Adv Mater ; 36(6): e2307613, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37848208

RESUMO

In infectious ischemic wounds, a lack of blood perfusion significantly worsens microbe-associated infection symptoms and frequently complicates healing. To overcome this daunting issue, antibacterial and angiogenic (2A) bio-heterojunctions (bio-HJs) consisting of CuS/MXene heterojunctions and a vascular endothelial growth factor (VEGF)-mimicking peptide (VMP) are devised and developed to accelerate infectious cutaneous regeneration by boosting angiogenesis via an endogenous-exogenous bistimulatory (EEB) strategy. Assisted by near-infrared irradiation, the bio-HJ platform exhibits versatile synergistic photothermal, photodynamic, and chemodynamic effects for robust antibacterial efficacy. In addition, copper ions liberated from 2A bio-HJs elevate VEGF secretion from fibroblasts, which provokes VEGF receptors (VEGFR) activation through an endogenous pathway, whereas VMP itself promotes an exogenous pathway to facilitate endothelial cell multiplication and tube formation by directly activating the VEGFR signaling pathway. Moreover, employing an in vivo model of infectious ischemic wounds, it is confirmed that the EEB strategy can considerably boost cutaneous regeneration through pathogen elimination, angiogenesis promotion, and collagen deposition. As envisaged, this work leads to the development of a powerful 2A bio-HJ platform that can serve as an effective remedy for bacterial invasion-induced ischemic wounds through the EEB strategy.


Assuntos
Fator A de Crescimento do Endotélio Vascular , Cicatrização , Pele , Colágeno , Antibacterianos/farmacologia
18.
Colloids Surf B Biointerfaces ; 234: 113640, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042109

RESUMO

A tannate-iron network-derived peroxidase-like catalyst loaded with Fe ions on carbon nitride (C3N4) was reported for detection of total antioxidant capacity (TAC) in food in this study. Metal-phenolic networks (MPNs) was employed to form a low coordination compound on C3N4, and calcined catalyst formed hollow structure with abundant and uniform Fe sites and surface folds. CN-FeC exhibited significant peroxidase-like activity and high substrate affinity. The homogeneous distribution of amorphous Fe elements on the C3N4 substrate provides more active sites, resulting in provided excellent catalytic activity to activate H2O2 to ·OH, 1O2 and O2·-. The established CN-FeC/TMB/H2O2 colorimetric system can detect AA in the concentration range of 5-40 µM, with the detection limits of 1.40 µM, respectively. It has good accuracy for the detection of vitamin C tablets, beverages. Taken together, this work shows that metal-phenolic networks can be an effective way to achieve efficient utilization of metal atoms and provides a promising idea for metal-phenolic networks in nanoparticle enzyme performance enhancement.


Assuntos
Antioxidantes , Nanopartículas , Peróxido de Hidrogênio/química , Peroxidase/química , Peroxidases/química , Nanopartículas/química , Colorimetria/métodos , Ferro
19.
Int J Biol Macromol ; 258(Pt 2): 128923, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38151088

RESUMO

Engineered collaborative biochemical techniques and regulated nanomaterials (NMs) offer extraordinary opportunities for improving the analysis performance of lateral flow immunoassay (LFIA). Herein, inspired by the ability of macromolecules (e.g., proteins) to assemble into new functional units and the remarkable optical performance of engineered regulated NMs, goat anti-mouse immunoglobulin (GAMI) serves as the "crosslinker" integrate with gold­manganese oxide (Au-MnOx) to assemble the "signal tracers (STs)-crosslinker-antibody (mAb)" for elevating the mAb utilization efficiency. Notably, the "STs-crosslinker-mAb" assembly shows ~13.33-folds mAb utilization efficiency enhance, which perfectly response the challenge between limited sensitivity and sufficient signal intensity in competitive-type LFIA. The black color and rough structure of Au-MnOx offer higher colorimetric brightness (~2-folds than AuNPs) and enhanced mAb coupling efficiency (up to 92.47%), which further improves sensitivity under the premise of functional assembly to intensify the competitive immunoreaction. Additionally, the convenient synthesis conditions (~13 min at room temperature) even comparable to direct purchase commercial products indicate that using Au-MnOx undoubtedly increases the cost-effectiveness. Encouragingly, the Au-MnOx-GAMI-mAb based LFIA exhibited high sensitivity (LOD: 0.063 ng mL-1 for clenbuterol (CLE) monitoring) by elevating mAb utilization efficiency with the attendant enhancing immune competition response in a cost-effective manner, which provides an invigorating reference pathway in point-of-care immunoassay.


Assuntos
Ouro , Nanopartículas Metálicas , Animais , Ouro/química , Cabras , Nanopartículas Metálicas/química , Imunoensaio/métodos , Anticorpos Monoclonais , Limite de Detecção
20.
World J Gastrointest Surg ; 15(10): 2320-2330, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37969709

RESUMO

BACKGROUND: Intra-abdominal infections (IAIs) is the most common type of surgical infection, with high associated morbidity and mortality rates. In recent years, due to the use of antibiotics, various drug-resistant bacteria have emerged, making the treatment of abdominal infections more challenging. Early surgical exploration can reduce the mortality of patients with abdominal infection and the occurrence of complications. However, available evidence regarding the optimal timing of IAI surgery is still weak. In study, we compared the effects of operation time on patients with abdominal cavity infection and tried to confirm the best timing of surgery. AIM: To assess the efficacy of early vs delayed surgical exploration in the treatment of IAI, in terms of overall mortality. METHODS: A systematic literature search was performed using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Ovid, and ScienceDirect. The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses method. Based on the timing of the surgical operation, we divided the literature into two groups: Early surgery and delayed surgery. For the early and delayed surgery groups, the intervention was performed with and after 12 h of the initial surgical intervention, respectively. The main outcome measure was the mortality rate. The literature search was performed from May 5 to 20, 2021. We also searched the World Health Organization International Clinical Trials Registry Platform search portal and ClinicalTrials.gov on May 20, 2021, for ongoing trials. This study was registered with the International Prospective Register of Systematic Reviews. RESULTS: We identified nine eligible trial comparisons. Early surgical exploration of patients with IAIs (performed within 12 h) has significantly reduced the mortality and complications of patients, improved the survival rate, and shortened the hospital stay. CONCLUSION: Early surgical exploration within 12 h may be more effective for the treatment of IAIs relative to a delayed operation.

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