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1.
Front Microbiol ; 15: 1390451, 2024.
Article de Anglais | MEDLINE | ID: mdl-39234539

RÉSUMÉ

Introduction: Hydrothermal vents, rich in heavy metals, provided a unique niche for heavy metal resistant microbes. However, knowledge about copper resistant microbes in deep sea hydrothermal vents is still limited. Methods: The copper-resistant bacteria were isolated from deep-sea hydrothermal vent samples and conducted thorough physical, phylogenetic, and genomic analyses to elucidate their copper resistance capability and related genes. Results: Twelve highly copper-resistant bacteria (up to 6-10 mM) were isolated from deep sea hydrothermal fields They were affiliated with the Pseudoalteromonas (4), Marinobacter (3), Halomonas (2), Psychrobacter (1), and Pseudomonas (1) genus in the α-Proteobacteria, and the Sphingomonas (1) genus in the ß-Proteobacteria. The presence of copper in the medium obviously induced the amount of polysaccharides and proteins in the crude extracellular polymeric substances (EPS) produced by Halomonas sp. CuT 3-1, Pseudoalteromonas sp. CuT 4-3 and Marinobacter metalliresistant CuT 6, which could absorb 40 to 50 mg•g-1 copper. We further described a novel species, Marinobacter metalliresistant sp. nov. CuT 6T, which exhibited a higher copper resistance and encoded more heavy metal resistance-related genes than other Marinobacter species. Discussion: It revealed that the copper resistance capability exhibited by these strains in hydrothermal fields is likely attributed to the production of exopolymeric substances, such as polysaccharides and proteins, as well as active transport or efflux mechanisms for heavy metals.

2.
Adv Mater ; : e2407570, 2024 Sep 03.
Article de Anglais | MEDLINE | ID: mdl-39224050

RÉSUMÉ

Carbonaceous materials hold great promise for K-ion batteries due to their low cost, adjustable interlayer spacing, and high electronic conductivity. Nevertheless, the narrow interlayer spacing significantly restricts their potassium storage ability. Herein, hierarchical N, S co-doped exfoliated holey graphene (NSEHG) with ultrahigh pyridinic/pyrrolic N (90.6 at.%) and large interlayer spacing (0.423 nm) is prepared through micro-explosion assisted thermal exfoliation of graphene oxide (GO). The underlying mechanism of the micro-explosive exfoliation of GO is revealed. The NSEHG electrode delivers a remarkable reversible capacity (621 mAh g-1 at 0.05 A g-1), outstanding rate capability (155 mAh g-1 at 10 A g-1), and robust cyclic stability (0.005% decay per cycle after 4400 cycles at 5 A g-1), exceeding most of the previously reported graphene anodes in K-ion batteries. In addition, the NSEHG electrode exhibits encouraging performances as anodes for Li-/Na-ion batteries. Furthermore, the assembled activated carbon||NSEHG potassium-ion hybrid capacitor can deliver an impressive energy density of 141 Wh kg-1 and stable cycling performance with 96.1% capacitance retention after 4000 cycles at 1 A g-1. This work can offer helpful fundamental insights into design and scalable fabrication of high-performance graphene anodes for alkali metal ion batteries.

3.
J Mater Chem B ; 12(35): 8488-8504, 2024 Sep 11.
Article de Anglais | MEDLINE | ID: mdl-39161280

RÉSUMÉ

Colloidal photonic crystals (CPCs), fabricated from the assembly of micro-/nano-particles, have attracted considerable interest due to their unique properties, such as structural color, slow-photon effect, and high specific surface area (SSA). Benefiting from these properties, significant progress has been made in the biological applications of CPCs. In this perspective, these properties and relative manipulation strategies are firstly discussed, building bridges between properties and biological applications of CPCs. Structural color endows CPCs with naked-eye sensing capability, which can be applied to physiological state assessment and diagnosis, as well as self-report of CPC-based diagnostic and therapeutic devices. The slow-photon effect contributes to enhanced fluorescence, surface-enhanced Raman scattering, and efficacy of photodynamic/photothermal therapy, when CPCs are combined with corresponding functional materials. High SSA provides CPCs with abundant binding sites and superior capabilities for loading, adsorption, delivery, etc. These properties can be utilized individually or synergistically to grant CPCs superior performance in biological applications. Next, the recent advancements of CPCs towards biological applications are summarized, including biosensors, wound dressings, cells-on-a-chip, and phototherapy. Finally, a perspective on the challenges and future development of CPCs for biological applications is presented.


Sujet(s)
Techniques de biocapteur , Colloïdes , Photons , Humains , Colloïdes/composition chimique , Animaux , Nanoparticules/composition chimique , Cristallisation , Propriétés de surface
4.
J Adv Res ; 2024 Aug 12.
Article de Anglais | MEDLINE | ID: mdl-39142440

RÉSUMÉ

INTRODUCTION: Homologous recombination repair during meiosis is essential for the exchange of genetic information between sister chromosomes, underpinning spermatogenesis and, consequently, fertility. The disruption of this process can lead to infertility, highlighting the importance of identifying the molecular actors involved. OBJECTIVES: This study aims to elucidate the role of the E3 ubiquitin ligase Rnf126 in spermatogenesis and its impact on fertility, particularly through its involvement in meiotic homologous recombination repair. METHODS: We used heterozygous and homozygous Rnf126 deletion models in mouse testes to examine the consequences on testicular health, sperm count, and the process of spermatogenesis. Additionally, we explored the association between RNF126 gene missense variants and nonobstructive male infertility in patients, with a focus on their functional impact on the protein's ubiquitin ligase activity. RESULTS: Rnf126 deletion led to testicular atrophy, disrupted seminiferous tubule structure, reduced sperm count, and spermatogenesis arrest at meiotic prophase I. Furthermore, male mice exhibited impaired homologous recombination repair and increased apoptosis within the seminiferous tubules. We identified four missense variants of the RNF126 (V68M, R241H, E261A, D253N) associated with male infertility. Specifically, the E261A and D253N variants, located in the RING domain, directly compromised the E3 ubiquitin ligase activity of RNF126. CONCLUSION: Our findings demonstrate the pivotal role of RNF126 in maintaining spermatogenesis and fertility, offering insights into the molecular mechanisms underlying male infertility. The identified RNF126 variants present novel targets for diagnostic and therapeutic strategies in treating nonobstructive male infertility.

5.
World J Gastroenterol ; 30(26): 3229-3246, 2024 Jul 14.
Article de Anglais | MEDLINE | ID: mdl-39086630

RÉSUMÉ

BACKGROUND: Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. AIM: To investigate the role of MOB3B in colorectal cancer (CRC). METHODS: This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results. RESULTS: MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts. CONCLUSION: Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.


Sujet(s)
Autophagie , Mouvement cellulaire , Tumeurs colorectales , Invasion tumorale , Transduction du signal , Sérine-thréonine kinases TOR , Sujet âgé , Animaux , Femelle , Humains , Mâle , Souris , Adulte d'âge moyen , Protéines adaptatrices de la transduction du signal/métabolisme , Protéines adaptatrices de la transduction du signal/génétique , Lignée cellulaire tumorale , Survie cellulaire , Tumeurs colorectales/anatomopathologie , Tumeurs colorectales/métabolisme , Tumeurs colorectales/génétique , Régulation négative , Régulation de l'expression des gènes tumoraux , Techniques de knock-down de gènes , Souris de lignée BALB C , Souris nude , Pronostic , Sérine-thréonine kinases TOR/métabolisme
6.
Small Methods ; : e2400513, 2024 Jul 23.
Article de Anglais | MEDLINE | ID: mdl-39039982

RÉSUMÉ

Hyaluronic acid (HA) is a naturally occurring polysaccharide found in the extracellular matrix with broad applications in disease treatment. HA possesses good biocompatibility, biodegradability, and the ability to interact with various cell surface receptors. Its wide range of molecular weights and modifiable chemical groups make it an effective drug carrier for drug delivery. Additionally, the overexpression of specific receptors for HA on cell surfaces in many disease states enhances the accumulation of drugs at pathological sites through receptor binding. In this review, the modification of HA with drugs, major receptor proteins, and the latest advances in receptor-targeted nano drug delivery systems (DDS) for the treatment of tumors and inflammatory diseases are summarized. Furthermore, the functions of HA with varying molecular weights of HA in vivo and the selection of drug delivery methods for different diseases are discussed.

7.
Nat Commun ; 15(1): 6209, 2024 Jul 23.
Article de Anglais | MEDLINE | ID: mdl-39043703

RÉSUMÉ

The Bin/Amphiphysin/Rvs (BAR) domain protein FAM92A1 is a multifunctional protein engaged in regulating mitochondrial ultrastructure and ciliogenesis, but its physiological role in the brain remains unclear. Here, we show that FAM92A1 is expressed in neurons starting from embryonic development. FAM92A1 knockout in mice results in altered brain morphology and age-associated cognitive deficits, potentially due to neuronal degeneration and disrupted synaptic plasticity. Specifically, FAM92A1 deficiency impairs diverse neuronal membrane morphology, including the mitochondrial inner membrane, myelin sheath, and synapses, indicating its roles in membrane remodeling and maintenance. By determining the crystal structure of the FAM92A1 BAR domain, combined with atomistic molecular dynamics simulations, we uncover that FAM92A1 interacts with phosphoinositide- and cardiolipin-containing membranes to induce lipid-clustering and membrane curvature. Altogether, these findings reveal the physiological role of FAM92A1 in the brain, highlighting its impact on synaptic plasticity and neural function through the regulation of membrane remodeling and endocytic processes.


Sujet(s)
Encéphale , Cognition , Souris knockout , Plasticité neuronale , Neurones , Synapses , Animaux , Encéphale/métabolisme , Neurones/métabolisme , Synapses/métabolisme , Plasticité neuronale/physiologie , Souris , Cognition/physiologie , Membrane cellulaire/métabolisme , Simulation de dynamique moléculaire , Humains , Phosphatidyl inositols/métabolisme , Cardiolipides/métabolisme , Mâle
8.
Cell Rep ; 43(8): 114529, 2024 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-39046876

RÉSUMÉ

Neuronal activation is required for the formation of drug-associated memory, which is critical for the development, persistence, and relapse of drug addiction. Nevertheless, the metabolic mechanisms underlying energy production for neuronal activation remain poorly understood. In the study, a large-scale proteomics analysis of lysine crotonylation (Kcr), a type of protein posttranslational modification (PTM), reveals that cocaine promoted protein Kcr in the hippocampal dorsal dentate gyrus (dDG). We find that Kcr is predominantly discovered in a few enzymes critical for mitochondrial energy metabolism; in particular, pyruvate dehydrogenase (PDH) complex E1 subunit α (PDHA1) is crotonylated at the lysine 39 (K39) residue through P300 catalysis. Crotonylated PDHA1 promotes pyruvate metabolism by activating PDH to increase ATP production, thus providing energy for hippocampal neuronal activation and promoting cocaine-associated memory recall. Our findings identify Kcr of PDHA1 as a PTM that promotes pyruvate metabolism to enhance neuronal activity for cocaine-associated memory.


Sujet(s)
Cocaïne , Hippocampe , Mémoire , Neurones , Pyruvate dehydrogenase (lipoamide) , Animaux , Cocaïne/pharmacologie , Neurones/métabolisme , Neurones/effets des médicaments et des substances chimiques , Pyruvate dehydrogenase (lipoamide)/métabolisme , Mémoire/effets des médicaments et des substances chimiques , Hippocampe/métabolisme , Hippocampe/effets des médicaments et des substances chimiques , Mâle , Souris , Souris de lignée C57BL , Maturation post-traductionnelle des protéines , Lysine/métabolisme , Humains
9.
Chin J Integr Med ; 2024 Jun 28.
Article de Anglais | MEDLINE | ID: mdl-38941044

RÉSUMÉ

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.

10.
Medicine (Baltimore) ; 103(25): e38567, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38905409

RÉSUMÉ

BACKGROUND: Our previous studies showed that laser moxibustion may be effective in alleviating the symptoms of knee osteoarthritis. However, the therapeutic effect in patients with different Kellgren-Lawrence (KL) grades is still unclear. We aimed to compare the efficacy of laser moxibustion in the treatment of knee osteoarthritis with different KL grades. METHODS: A total of 392 symptomatic KOA patients with different KL grades were randomly assigned to the laser treatment or sham laser control group (1:1). The patients received laser moxibustion treatment or sham treatment 3 times a week for 4 weeks. Outcomes were measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and Visual Analog Scale (VAS) scores, and the primary outcome measurement was the change in WOMAC pain scores from baseline to week 4. RESULTS: Among 392 randomized participants, 364 (92.86%) completed the trial. Participants with KL grades 2, 3, and 4 had significantly higher pain, functional, and total WOMAC scores than those with KL grade 1. Spearman correlation test results showed a positive correlation between KL grade and WOMAC pain, function, stiffness scores, and WOMAC total scores. That is, the higher the KL grade, the higher the WOMAC pain, function, stiffness, and WOMAC total scores. After 4 weeks of treatment, patients with KL grades 2 and 3 had significantly higher improvement scores in pain, function, and total scores than those with KL grade 1, whereas those with KL grade 2 had significantly higher improvement scores in stiffness than those with KL grade 1. Patients with KL grade 4 showed no significant effects after laser moxibustion treatment. CONCLUSION: Laser moxibustion is effective for pain reduction and functional improvement in the treatment of KOA with KL grades 2 and 3.


Sujet(s)
Moxibustion , Gonarthrose , Mesure de la douleur , Humains , Gonarthrose/thérapie , Moxibustion/méthodes , Femelle , Mâle , Adulte d'âge moyen , Sujet âgé , Résultat thérapeutique , Indice de gravité de la maladie , Thérapie laser/méthodes
11.
Nanomicro Lett ; 16(1): 224, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38888701

RÉSUMÉ

Organic photovoltaics (OPVs) need to overcome limitations such as insufficient thermal stability to be commercialized. The reported approaches to improve stability either rely on the development of new materials or on tailoring the donor/acceptor morphology, however, exhibiting limited applicability. Therefore, it is timely to develop an easy method to enhance thermal stability without having to develop new donor/acceptor materials or donor-acceptor compatibilizers, or by introducing another third component. Herein, a unique approach is presented, based on constructing a polymer fiber rigid network with a high glass transition temperature (Tg) to impede the movement of acceptor and donor molecules, to immobilize the active layer morphology, and thereby to improve thermal stability. A high-Tg one-dimensional aramid nanofiber (ANF) is utilized for network construction. Inverted OPVs with ANF network yield superior thermal stability compared to the ANF-free counterpart. The ANF network-incorporated active layer demonstrates significantly more stable morphology than the ANF-free counterpart, thereby leaving fundamental processes such as charge separation, transport, and collection, determining the device efficiency, largely unaltered. This strategy is also successfully applied to other photovoltaic systems. The strategy of incorporating a polymer fiber rigid network with high Tg offers a distinct perspective addressing the challenge of thermal instability with simplicity and universality.

12.
Reprod Biomed Online ; 49(3): 103991, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38936339

RÉSUMÉ

RESEARCH QUESTION: Does routine clinical practice require an increase in the resolution of preimplantation genetic testing for aneuploidies (PGT-A) to detect segmental aneuploidies ≤5 Mb? DESIGN: This retrospective study analysed 963 trophectoderm biopsies from 346 couples undergoing PGT between 2019 and 2023. Segmental aneuploidies ≥1 Mb were reported. The characteristics, clinical interpretation and concordance of segmental aneuploidies ≤5 Mb were analysed. RESULTS: The incidence of segmental aneuploidies was 15.1% (145/963) in blastocysts, with segmental aneuploidies of ≤5 Mb accounting for 2.3% (22/963). The size of the segmental aneuploidies showed a skewed distribution. Segmental aneuploidies ≤5 Mb were found to occur more frequently on the q arm of the chromosome, compared with the p arm. Losses of ≤5 Mb segmental aneuploidies were more prevalent than gains, with 17 deletions compared with 5 duplications. Of the segmental aneuploidies, 63.6% (14/22) ≤5 Mb were de novo, and 50.0% (7/14) of de-novo segmental aneuploidies were pathogenic/likely pathogenic (P/LP) copy number variations, accounting for 0.7% of 963 blastocysts. For blastocysts carrying ≤5 Mb segmental aneuploidies, a re-analysis of back-up biopsy samples showed that 35.7% of de-novo segmental aneuploidies (5/14) were not detected in the back-up samples. Cases were reported in which prenatal diagnosis (amniocentesis) revealed the absence of embryonic ≤5 Mb segmental aneuploidies detected at the blastocyst stage. CONCLUSIONS: The incidence of P/LP de-novo ≤5 Mb segmental aneuploidies in human blastocysts is extremely low. There is no compelling need to increase the resolution of PGT-A to 5 Mb in routine clinical practice.


Sujet(s)
Aneuploïdie , Dépistage génétique , Diagnostic préimplantatoire , Humains , Diagnostic préimplantatoire/méthodes , Études rétrospectives , Femelle , Adulte , Dépistage génétique/méthodes , Grossesse , Mâle , Blastocyste
13.
Ecotoxicol Environ Saf ; 278: 116441, 2024 Jun 15.
Article de Anglais | MEDLINE | ID: mdl-38733805

RÉSUMÉ

Oxybenzone (OBZ; benzophenone-3, CAS# 131-57-7), as a new pollutant and ultraviolet absorbent, shows a significant threat to the survival of phytoplankton. This study aims to explore the acute toxic effects of OBZ on the growth of the microalga Selenastrum capricornutum, as well as the mechanisms for its damage to the primary metabolic pathways of photosynthesis and respiration. The results demonstrated that the concentrations for 50 % of maximal effect (EC50) of OBZ for S. capricornutum were 9.07 mg L-1 and 8.54 mg L-1 at 72 h and 96 h, respectively. A dosage of 4.56 mg L-1 OBZ significantly lowered the photosynthetic oxygen evolution rate of S. capricornutum in both light and dark conditions for a duration of 2 h, while it had no effect on the respiratory oxygen consumption rate under darkness. OBZ caused a significant decline in the efficiency of photosynthetic electron transport due to its damage to photosystem II (PSII), thereby decreasing the photosynthetic oxygen evolution rate. Over-accumulated H2O2 was produced under light due to the damage caused by OBZ to the donor and acceptor sides of PSII, resulting in increased peroxidation of cytomembranes and inhibition of algal respiration. OBZ's damage to photosynthesis and respiration will hinder the conversion and reuse of energy in algal cells, which is an important reason that OBZ has toxic effects on S. capricornutum. The present study indicated that OBZ has an acute toxic effect on the microalga S. capricornutum. In the two most important primary metabolic pathways in algae, photosynthesis is more sensitive to the toxicity of OBZ than respiration, especially in the dark.


Sujet(s)
Benzophénones , Microalgues , Photosynthèse , Produits antisolaires , Photosynthèse/effets des médicaments et des substances chimiques , Benzophénones/toxicité , Microalgues/effets des médicaments et des substances chimiques , Produits antisolaires/toxicité , Polluants chimiques de l'eau/toxicité , Peroxyde d'hydrogène/métabolisme , Complexe protéique du photosystème II/métabolisme , Complexe protéique du photosystème II/effets des médicaments et des substances chimiques , Rayons ultraviolets , Transport d'électrons/effets des médicaments et des substances chimiques
14.
Chin J Integr Med ; 30(6): 489-498, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38801641

RÉSUMÉ

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).


Sujet(s)
Médecine traditionnelle chinoise , Tumeurs de l'estomac , Humains , Tumeurs de l'estomac/traitement médicamenteux , Tumeurs de l'estomac/mortalité , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/thérapie , Mâle , Femelle , Adulte d'âge moyen , Analyse de survie , Médecine traditionnelle chinoise/méthodes , Sujet âgé , Chine/épidémiologie , Score de propension , Adulte
15.
Int J Biol Macromol ; 269(Pt 2): 131795, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38670175

RÉSUMÉ

Bacterial infections during wound healing impede the healing process and trigger local or systemic inflammatory reactions. Consequently, there is an urgent need to develop a new material with antimicrobial and antioxidant properties to promote infected wound healing. A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel (HMn) is prepared by employing MnO2 nanosheets into 4ARM-PEG5000-SH crosslinked methacrylated hyaluronic acid (HAMA) network. The coordination between sulfhydryl groups of 4ARM-PEG5000-SH and MnO2 nanosheets ensures entrapment of the nanosheets within the hydrogel, while the interaction between 4ARM-PEG5000-SH and HAMA results in facile gelation through thiol-ene click reaction. MnO2 nanosheets exhibit strong photothermal properties and reactive oxygen species (ROS) scavenging abilities, while hyaluronic acid promotes wound healing. When subjected to near-infrared (NIR) irradiation, the HMn achieves a bactericidal rate of 95.24 % for Staphylococcus aureus and nearly 100 % for Escherichia coli. In animal experiments, treatment with the HMn under NIR irradiation results in the best wound healing outcomes. Both in vitro and vivo biocompatible assays demonstrate that the HMn has rarely cell cytotoxicity and tissue damage. The HMn is easy to prepare and has good biocompatibility as well as efficient antibacterial and antioxidant properties, providing a novel method for the treatment of infected wounds.


Sujet(s)
Antioxydants , Escherichia coli , Acide hyaluronique , Hydrogels , Staphylococcus aureus , Cicatrisation de plaie , Acide hyaluronique/composition chimique , Acide hyaluronique/pharmacologie , Hydrogels/composition chimique , Hydrogels/pharmacologie , Antioxydants/pharmacologie , Antioxydants/composition chimique , Animaux , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Staphylococcus aureus/effets des médicaments et des substances chimiques , Escherichia coli/effets des médicaments et des substances chimiques , Infection de plaie/traitement médicamenteux , Infection de plaie/microbiologie , Antibactériens/pharmacologie , Antibactériens/composition chimique , Souris , Espèces réactives de l'oxygène/métabolisme , Anti-infectieux/pharmacologie , Anti-infectieux/composition chimique , Humains , Synergie des médicaments
16.
Article de Anglais | MEDLINE | ID: mdl-38558503

RÉSUMÉ

The blood-brain barrier presents a key limitation to the administration of therapeutic molecules for the treatment of brain disease. While drugs administered orally or intravenously must cross this barrier to reach brain targets, the unique anatomical structure of the olfactory system provides a route to deliver drugs directly to the brain. Entering the brain via receptor, carrier, and adsorption-mediated transcytosis in the nasal olfactory and trigeminal regions has the potential to increase drug delivery. In this review, we introduce the physiological and anatomical structures of the nasal cavity, and summarize the possible modes of transport and the relevant receptors and carriers in the nose-to-brain pathway. Additionally, we provide examples of nanotherapeutics developed for intranasal drug delivery to the brain. Further development of nanoparticles that can be applied to intranasal delivery systems promises to improve drug efficacy and reduce drug resistance and adverse effects by increasing molecular access to the brain. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.


Sujet(s)
Encéphale , Nanoparticules , Encéphale/métabolisme , Barrière hémato-encéphalique/métabolisme , Administration par voie nasale , Préparations pharmaceutiques , Systèmes de délivrance de médicaments , Nanoparticules/composition chimique
17.
Nat Commun ; 15(1): 2831, 2024 Apr 02.
Article de Anglais | MEDLINE | ID: mdl-38565562

RÉSUMÉ

The prodrug design strategy offers a potent solution for improving therapeutic index and expanding drug targets. However, current prodrug activation designs are mainly responsive to endogenous stimuli, resulting in unintended drug release and systemic toxicity. In this study, we introduce 3-vinyl-6-oxymethyl-tetrazine (voTz) as an all-in-one reagent for modular preparation of tetrazine-caged prodrugs and chemoselective labeling peptides to produce bioorthogonal activable peptide-prodrug conjugates. These stable prodrugs can selectively bind to target cells, facilitating cellular uptake. Subsequent bioorthogonal cleavage reactions trigger prodrug activation, significantly boosting potency against tumor cells while maintaining exceptional off-target safety for normal cells. In vivo studies demonstrate the therapeutic efficacy and safety of this prodrug design approach. Given the broad applicability of functional groups and labeling versatility with voTz, we foresee that this strategy will offer a versatile solution to enhance the therapeutic range of cytotoxic agents and facilitate the development of bioorthogonal activatable biopharmaceuticals and biomaterials.


Sujet(s)
Composés hétérocycliques , Promédicaments , Promédicaments/pharmacologie , Promédicaments/usage thérapeutique , Lignée cellulaire tumorale , Cystéine , Systèmes de délivrance de médicaments
19.
J Colloid Interface Sci ; 665: 742-751, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38554464

RÉSUMÉ

In this paper, we have developed a simple and efficient sulfur-amine chemistry strategy to prepare a three-dimensional (3D) porous Ti3C2Tx composite with large amounts of N and S terminal groups. The well-designed 3D macroporous architecture presents enlarged interlayer spacing, large specific surface area, and unique porous structure, which successfully solves the re-stacking issue of MXene during storage and electrode fabrication. It is the amount of concentrated hydrochloric acid added to the S-EDA (ethylenediamine)/MXene colloidal suspension that is critical to the formation of 3D morphology. In addition, N and S terminals on MXene could improve the adsorption ability of K+. Owing to the synergistic effect of the structure design and terminal modification, the N, S codoped three-dimensional porous Ti3C2Tx (3D-NSPM) material shows a high surface capacitive contribution and rapid diffusion kinetics for K+ and Na+. As a result, the as-prepared 3D-NSPM delivers high reversible capacity (237 and 273 mAh g-1 at 0.1 A g-1 for PIBs and SIBs, respectively), superb cycling stability (84.9% capacity retention after 10,000 cycles at 1 A g-1 in PIBs and 74.0% capacity retention after 2200 cycles at 1 A g-1 in SIBs), and excellent rate capability (111 and 196 mAh g-1 at 5 A g-1 for PIBs and SIBs, respectively), which are superior to other MXene-based anodes for PIBs and SIBs. Moreover, the described strategy provides a new insight for constructing the 3D porous structure from 2D building blocks beyond MXene.

20.
Adv Drug Deliv Rev ; 207: 115219, 2024 04.
Article de Anglais | MEDLINE | ID: mdl-38401847

RÉSUMÉ

Emerging evidence suggests that vascular pathological changes play a pivotal role in the pathogenesis of Alzheimer's disease (AD). The dysfunction of the cerebral vasculature occurs in the early course of AD, characterized by alterations in vascular morphology, diminished cerebral blood flow (CBF), impairment of the neurovascular unit (NVU), vasculature inflammation, and cerebral amyloid angiopathy. Vascular dysfunction not only facilitates the influx of neurotoxic substances into the brain, triggering inflammation and immune responses but also hampers the efflux of toxic proteins such as Aß from the brain, thereby contributing to neurodegenerative changes in AD. Furthermore, these vascular changes significantly impact drug delivery and distribution within the brain. Therefore, developing targeted delivery systems or therapeutic strategies based on vascular alterations may potentially represent a novel breakthrough in AD treatment. This review comprehensively examines various aspects of vascular alterations in AD and outlines the current interactions between nanoparticles and pathological changes of vascular.


Sujet(s)
Maladie d'Alzheimer , Nanoparticules , Humains , Maladie d'Alzheimer/traitement médicamenteux , Maladie d'Alzheimer/métabolisme , Peptides bêta-amyloïdes/métabolisme , Encéphale/anatomopathologie , Inflammation
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