Nanozymes have captured significant attention as a versatile and promising alternative to natural enzymes in catalytic applications, with wide-ranging implications for both diagnosis and therapy. ...However, the limited selectivity exhibited by many nanozymes presents challenges to their efficacy in diagnosis and raises concerns regarding their impact on the progression of disease treatments. In this article, we explore the latest innovations aimed at enhancing the selectivity of nanozymes, thereby expanding their applications in theranostic nanoplatforms. We place paramount importance on the critical development of highly selective nanozymes and present innovative strategies that have yielded remarkable outcomes in augmenting selectivities. The strategies encompass enhancements in analyte selectivity by incorporating recognition units, refining activity selectivity through the meticulous control of structural and elemental composition, integrating synergistic materials, fabricating selective nanomaterials, and comprehensively fine-tuning selectivity
via
approaches such as surface modification, cascade nanozyme systems, and manipulation of external stimuli. Additionally, we propose optimized approaches to propel the further advancement of these tailored nanozymes while considering the limitations associated with existing techniques. Our ultimate objective is to present a comprehensive solution that effectively addresses the limitations attributed to non-selective nanozymes, thus unlocking the full potential of these catalytic systems in the realm of theranostics.
This work explores cutting-edge strategies to enhance nanozyme selectivity, vital for improving diagnostics and treatments, unlocking their full theranostic potential.
Traditional cancer diagnosis strategies are not considered by most people until the last resort, which delays many cancer treatments leading to advanced stages. Tumor marker sensors show great ...potential for detecting cancer because of its cost-effective and harmless checking procedures. Normally, one tumor marker is detected each time by using one type of sensor, but the accuracy to declare cancer is not always satisfied. Metal nanoclusters are ultra-small nanomaterials with low toxicity, distinct optical properties, catalytic activities, and cost-effective performance. Some metal nanoclusters have been designed to detect more than one tumor marker in a single step. The consideration of combined parameters using such facile sensing strategies has the potential to simplify the test procedure, and increase the diagnostic accuracy of early cancer. Therefore, various sensing strategies for the multiplex detection of tumor markers using metal nanoclusters are summarized.
Scheme for the multiplex detection of tumor markers based on specific, Chem-nose and label-free sensing.
Spinal cord injury (SCI) leads to neuronal death resulting in central nervous system (CNS) dysfunction; however, the pathogenesis is still poorly understood. Melatonin (MT), a hormone secreted mainly ...by the pineal gland, is associated with neuroprotective effects against SCI. Enhanced autophagy can promote the recovery of locomotor function and reduce apoptosis after SCI. Interestingly, MT increases autophagy in SCI in vivo. Nevertheless, the ability of MT to increase autophagy and decrease apoptosis, and the potential effects on the recovery of motor neurons in the anterior horn after SCI remain to be clarified. In this study, we discovered that MT treatment improved motor function recovery in a rat SCI model. Indeed, MT upregulated the expression of the phosphatidylinositol 3-kinase (PI3K), while expression of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) was downregulated after SCI. Additionally, MT increased the expression of autophagy-activating proteins, while the expression of apoptosis-activating proteins in neurons was decreased following SCI. Furthermore, autophagy was inhibited, while apoptosis was induced in SCI model rats and lipopolysaccharide (LPS)-stimulated primary neurons by treatment with MT, the PI3K inhibitor 3-methyladenine (3-MA) and mTOR inhibitor Rapamycin (Rapa). Collectively, our results suggest that MT can improve the recovery of locomotor function by enhancing autophagy as well as reducing apoptosis after SCI in rats, probably via the PI3K/AKT/mTOR signaling pathway.
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•The photothermal combination strategy based on EGCG and gold nanoparticles is a new attempt at periodontal bone repair.•EGCG combined with gold nanoparticles as a nanoplatform for ...periodontal disease bone repair and inhibition of oral bacterial infection.•The obtained hydrogel nanoplatform achieved an effective sterilization rate and promoted osteogenesis by promoting angiogenesis.
Periodontitis caused by bacteria is the most common oral disease. In the face of plaque formation, traditional scaling and antibiotic treatment can lead to gum recession, drug resistance and other side effects. The nanoplatform of multifunctional complex treatment is attractive for the treatment of periodontitis. In this study, epigallocatechin gallate (EGCG) was loaded into gold nanoparticle-modified hydrogels (E-Au@H) to achieve the synergistic functions of near-infrared (NIR) photosensitization, bactericidal and periodontal tissue regeneration. E-Au@H rapidly heats up to 50.7 °C within 5 min under NIR light irradiation, exerting a good photothermal effect, while the NIR spectrum can effectively control the release of tea polyphenols, enhance the antibacterial effect, promote angiogenesis and improve bone regeneration. In vitro studies showed that NIR-irradiated composites inhibited S. aureus, E. coli and S. aureus biofilms by 94 %, 92 % and 74 %, increased alkaline phosphatase activity 5-fold after 7 days and increased extracellular matrix mineralization rate 3-fold after 21 days. The rat periodontitis model successfully demonstrated that E-Au@H with NIR light irradiation inhibited dental plaque biofilm by 87 % and promoted alveolar bone regeneration by 38 %. The experimental results suggest that this hydrogel with a NIR-sensitive composite nanoplatform offers new possibilities for the treatment of periodontal disease.
The COVID-19 pandemic caused by SARS-CoV-2 has been identified as a culprit in the development of a variety of disorders, including arthritis. Although the emergence of arthritis following SARS-CoV-2 ...infection may not be immediately discernible, its underlying pathogenesis is likely to involve a complex interplay of infections, oxidative stress, immune responses, abnormal production of inflammatory factors, cellular destruction,
etc
. Fortunately, recent advancements in nanozymes with enzyme-like activities have shown potent antiviral effects and the ability to inhibit oxidative stress and cytokines and provide immunotherapeutic effects while also safeguarding diverse cell populations. These adaptable nanozymes have already exhibited efficacy in treating common types of arthritis, and their distinctive synergistic therapeutic effects offer great potential in the fight against arthritis associated with COVID-19. In this comprehensive review, we explore the potential of nanozymes in alleviating arthritis following SARS-CoV-2 infection by neutralizing the underlying factors associated with the disease. We also provide a detailed analysis of the common therapeutic pathways employed by these nanozymes and offer insights into how they can be further optimized to effectively address COVID-19-associated arthritis.
Nanozymes, with functions such as virus disinfection, oxidative stress reduction, cytokine production regulation, and inflammation reduction, may be a promising treatment for COVID-19-related arthritis linked to shared factors.
High level apoptosis induced by spinal cord injury (SCI) evokes serious damage because of the loss and dysfunction of motor neurons. Our previous studies showed that inhibition of autophagy evokes ...the activation of apoptosis. Interestingly, Baicalein, a medicine with anti-apoptosis activity that is derived from the roots of herb Scutellaria baicalensis, largely induces autophagy by activating phosphatidylinositol 3-kinase (PI3K). In this study, we investigated the effects of intraperitoneal injection of Baicalein on autophagy and apoptosis in SCI mice and evaluated the relationship between autophagy and apoptosis. We demonstrated that Baicalein promoted the functional recovery of motor neurons at 7 d after SCI. In addition, Baicalein enhanced neuronal autophagy and the autophagy-related factor PI3K, while inhibiting the p62 protein. Baicalein treatment decreased neuronal apoptosis at 7 d after SCI. Moreover, when inhibiting autophagy, apoptosis was upgraded by Baicalein treatment after injury. Thus, Baicalein attenuated SCI by inducing autophagy to reduce apoptosis in neurons potentially via activating PI3K.
Acute myeloid leukaemia (AML) is a fatal haematopoietic malignancy and is treated with the conventional combination of cytarabine (Ara-C) and daunorubicin (Dau). The survival rate of AML patients is ...lower due to the cardiotoxicity of daunorubicin. Clinically, homoharringtonine (HHT) plus Ara-C has been reported to be equally effective as Dau plus Ara-C in some types of AML patients with less toxic effects. We utilized the clinical use of homoharringtonine in combination with Ara-C to test its combination mechanism. We found that the insensitivity of AML cells to cytarabine-induced apoptosis is associated with increased Mcl-1 stability and p38 inactivation. HHT downregulates Mcl-1, phosphorylates H2AX and induces apoptosis by activating p38 MAPK. Inactivation of p38 through inhibitors and siRNA blocks apoptosis, H2AX phosphorylation and Mcl-1 reduction. HHT enhances Ara-C activation of the p38 MAPK signalling pathway, overcoming Ara-C tolerance to cell apoptosis by regulating the p38/H2AX/Mcl-1 axis. The optimal ratio of HHT to Ara-C for synergistic lethality in AML cells is 1:4 (M/M). HHT synergistically induces apoptosis in combination with Ara-C in vitro and prolongs the survival of xenografts. We provide a new mechanism for AML treatment by regulating the p38 MAPK/H2AX/Mcl-1 axis to improve cytarabine therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Spinal cord injury (SCI) is one of the most serious nervous system disorders characterised by high morbidity and disability. Inflammatory and autophagy responses play an important role in the ...development of SCI. Metformin, a first-line drug for type-2 diabetes, features autophagy promotion as well as anti-inflammatory and anti-apoptotic properties in the nervous system. In this study, we investigated the neuroprotection effects of metformin preconditioning on rats after SCI. Results of Basso, Beattie and Bresnahan scores, HE staining and Nissl staining showed that the function and quantity of motor neurons were protected by metformin after SCI. Western blot revealed that the expression of Beclin-1 and LC3B-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI. Metformin significantly reduced the expression of NF-κB. Moreover, Western blot and immunofluorescence results indicated that caspase 3 activation was reduced, whereas bcl-2 level was significantly increased by metformin. Hence, metformin attenuated SCI by inhibiting apoptosis and inflammation and enhancing the autophagy via the mTOR/p70S6K signalling pathway.
•Metformin preconditioning provide neuroprotection through enhancement of autophagy.•Metformin preconditioning induces autophagy via mTOR signalling pathway.•Metformin preconditioning reduced NF-κB-mediated inflammation.•Metformin preconditioning promotes the recovery of motor nerve function after SCI.
Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the ...differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.
Graphical Abstract
Downregulation of UHRF1 promotes the recovery of motor function in mice with spinal cord injury. By analyzing the RNA sequencing results of mice with spinal cord injury for 3 days and selecting UHRF1 for experimental validation, the study found that inhibiting UHRF1 can promote motor function recovery.
Implant-associated infections in orthopaedic surgeries are very critical as they may hinder bone healing, cause implant failure and even progress to osteomyelitis. Drug-eluting implants for local ...delivery of antibiotics at surgical sites are thought to be promising in preventing infections. Herein, the antibiotic vancomycin was encapsulated in a poly(ethylene glycol) (PEG)-based hydrogel film that was covalently bound to Ti implants and subsequently covered by a PEG-poly(lactic-
co
-caprolactone) (PEG-PLC) membrane. Additionally, crosslinked starch (CSt) was mixed with the hydrogel because its porous microstructure is able to inhibit hydrogel swelling and thus slow down drug release. The release behavior could be regulated by the drug loading and the coating thickness. The vancomycin-loaded Ti implants showed no initial burst release, offering a sustained drug release for nearly 3 weeks
in vitro
and more than 4 weeks
in vivo
. In a rabbit model of
S. aureus
infection, the implants with a 4 mg vancomycin loading significantly reduced the inflammatory reaction and exhibited a good antimicrobial capability. The immobilization of the antibiotic-loaded polymeric coatings on orthopaedic implants can offer a sustainable drug release with no initial burst release and maintain an effective concentration for a longer time, so it is expected to be an effective strategy to treat and prevent local bone infections.
Polymeric multilayers covalently fixed to Ti surfaces could offer a sustained drug release with no initial burst release and extend the drug release time.
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