RESUMO
Among neoplasia-associated epigenetic alterations, changes in cellular glycosylation have recently received attention as a key component of hematological malignancy progression. Alterations in glycosylation appear to not only directly impact cell growth and survival, but also alter the adhesion of tumor cells and their interactions with the microenvironment, facilitating cancer-induced immunomodulation and eventual metastasis. Changes in glycosylation arise from altered expression of glycosyltransferases, enzymes that catalyze the transfer of saccharide moieties to a wide range of acceptor substrates, such as proteins, lipids, and other saccharides in the endoplasmic reticulum (ER) and Golgi apparatus. Novel glycan structures in hematological malignancies represent new targets for the diagnosis and treatment of blood diseases. This review summarizes studies of the aberrant expression of glycans commonly found in hematological malignancies and their potential mechanisms and defines the specific roles of glycans as drivers or passengers in the development of hematological malignancies.
Assuntos
Glicosiltransferases , Neoplasias Hematológicas , Células Sanguíneas/metabolismo , Glicosilação , Glicosiltransferases/metabolismo , Humanos , Polissacarídeos , Microambiente TumoralRESUMO
Psoriasis is an incurable inflammatory skin disease that is mediated by the immune system. Although kaempferol has been known for its anti-inflammatory, antioxidant, and anticancer properties, its therapeutic effectiveness is often limited due to its poor water solubility and low bioavailability. To address these challenges, we developed a promising kaempferol hydrogel (DK-pGEL) using Pluronic F127 and a deep eutectic solvent (DES) with varying concentrations of kaempferol. In this study, we first evaluated the rheological properties and viscosity of the DK-pGEL hydrogel. The G' of DK-pGEL (â¼14 kPa) hydrogels was significantly lower than the control group (â¼30 kPa) at 37 °C. The DK-pGEL hydrogel exhibited ideal fluidity and viscosity at 37 °C, as demonstrated by its shear-thinning behavior. Moreover, the DK-pGEL hydrogel showed controlled release characteristics with a drug release of 97.43 ± 5.37 µg/mL over 60 h. Furthermore, in vitro antioxidant experiments revealed that DK-pGEL exhibited significant radical scavenging ability against the DPPH-radical (96.27 ± 0.37%), ABTS-radical (98.11 ± 0.79%), hydroxyl-radical (66.36 ± 1.01%), and superoxide-radical (90.52 ± 0.79%) at a concentration of 250 µg/mL kaempferol. Additionally, DK-pGEL exhibited notable cellular antioxidant effects by inhibiting reactive oxygen species generation. Cell viability assays (CCK8) and live/dead cell assays were conducted to assess the cytotoxicity of DK-pGEL. The results showed that DK-pGEL could effectively inhibit HaCaT cell proliferation without causing significant cytotoxicity. To evaluate the therapeutic potential of DK-pGEL, an imiquimod (IMQ)-induced mouse model of psoriasis-like lesions was employed. Remarkably, the DK-pGEL hydrogel could significantly reduce the psoriasis area and severity index score, improve the histopathology induced by IMQ, and downregulate the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-17A) in the skin tissue. These findings demonstrate that the DES-assisted kaempferol hydrogel holds promise as a topical drug delivery system for psoriasis treatment.
Assuntos
Solventes Eutéticos Profundos , Psoríase , Animais , Camundongos , Hidrogéis , Antioxidantes/uso terapêutico , Quempferóis/farmacologia , Inflamação/tratamento farmacológico , Psoríase/tratamento farmacológico , Pele , Imiquimode , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
Burn wound healing continues to pose significant challenges due to excessive inflammation, the risk of infection, and impaired tissue regeneration. In this regard, an antibacterial, antioxidant, and anti-inflammatory nanocomposite (called HPA) that combines a nanosystem using hexachlorocyclotriphosphazene and the natural polyphenol of Phloretin with silver nanoparticles (AgNPs) is developed. HPA effectively disperses AgNPs to mitigate any toxicity caused by aggregation while also showing the pharmacological activities of Phloretin. During the initial stage of wound healing, HPA rapidly releases silver ions from its surface to suppress bacterial activity. Moreover, these nanoparticles are pH-sensitive and degrade efficiently in the acidic infection microenvironment, gradually releasing Phloretin. This sustained release of Phloretin helps scavenge overexpressed reactive oxygen species in the infected microenvironment area, thus reducing the upregulation of pro-inflammatory cytokines. The antibacterial activity, free radical clearance, and regulation of inflammatory factors of HPA through in vitro experiments are validated. Additionally, its effects using an infectious burn mouse model in vivo are evaluated. HPA is found to promote collagen deposition and epithelialization in the wound area. With its synergistic antibacterial, antioxidant, and anti-inflammatory activities, as well as favorable biocompatibilities, HPA shows great promise as a safe and effective multifunctional nanoplatform for burn injury wound dressings.
Assuntos
Anti-Infecciosos , Queimaduras , Nanopartículas Metálicas , Infecção dos Ferimentos , Camundongos , Animais , Prata/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Antibacterianos/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Queimaduras/tratamento farmacológico , FloretinaRESUMO
Nanozymes are considered as the promising antimicrobial agents due to the enzyme-like activity for chemo-dynamic therapy (CDT). However, it remains a challenge to develop novel nanozyme systems for achieving stimuli-responsive, and efficient nanozyme catalysis with multimodal synergistic enhancement. In this work, a near-infrared (NIR) plasmonic-enhanced nanozyme catalysis and photothermal performance for effective antimicrobial applications are proposed. A Ti3 C2 MXene/Fe-MOFs composite (MXM) with NIR plasmonic-enhanced CDT combined with photothermal properties is successfully developed by loading metal-organic framework (MOF) nanozymes onto Ti3 C2 MXene. The mechanism of NIR induced localized surface plasmon resonance (LSPR)-enhanced CDT and photothermal therapy (PTT) is well explained through activation energy (Ea ), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), fluorescence analysis experiments, and finite element simulation. It reveals that MXene nanosheets exhibit NIR plasmon exciters and generate hot electrons that can transfer to the surface of Fe-MOFs, promoting the Fenton reaction and enhances CDT. While the photothermal heating of MXene produced by LSPR can also boost the CDT of Fe-MOFs under NIR irradiation. Both in vitro and in vivo experimental results demonstrate that LSPR-induced MXM system has outstanding antimicrobial properties, can promote angiogenesis and collagen deposition, leading to the accelerated wound healing.
Assuntos
Anti-Infecciosos , Estruturas Metalorgânicas , Neoplasias , Nitritos , Elementos de Transição , Humanos , Estruturas Metalorgânicas/química , Ressonância de Plasmônio de Superfície , Neoplasias/terapia , Linhagem Celular TumoralRESUMO
The choice of hemostatic technique is a curial concern for surgery and as first-aid treatment in combat. To treat uncontrolled bleeding in complex wound environments, chitosan-based hemostatic sponges have attracted significant attention in recent years because of the excellent biocompatibility, degradability, hemostasis and antibacterial properties of chitosan and their unique sponge-like morphology for high fluid absorption rate and priority aggregation of blood cells/platelets to achieve rapid hemostasis. In this review, we provide a historical perspective on the use of chitosan hemostatic sponges as the new generation of hemostatic materials for uncontrolled bleeding emergencies in complex wounds. We summarize the modification of chitosan, review the current status of preparation protocols of chitosan sponges based on various composite systems, and highlight the recent achievements on the detailed breakdown of the existing chitosan sponges to present the relationship between their composition, physical properties, and hemostatic capacity. Finally, the future opportunities and challenges of chitosan hemostatic sponges are also proposed.
Assuntos
Quitosana , Hemostáticos , Humanos , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Quitosana/uso terapêutico , Hemostasia , Hemorragia/tratamento farmacológico , PlaquetasRESUMO
The Actinomycete strain P294 was isolated from soil and identified as Streptomyces sp. based upon the results of 16S rRNA sequence analysis. Three compounds obtained from the solid fermentation products of this strain have been determined by 1D, 2D NMR and HRMS experiments. These compounds include two new compounds angumycinones C (1) and D (2), and the known compound X-14881 E (3). All compounds were assayed for antibacterial and nematicidal activity. The results showed the three compounds had different degrees of inhibitory activity against several target bacteria but no significant toxicity against the nematode Caenorhabditis elegans.