Hypoxic pulmonary hypertension (HPH) is a life-threatening disease that occurs due to a lack of oxygen in the lungs, leading to an increase in pulmonary vascular resistance, right ventricular failure, and ultimately death. HPH is a multifactorial disorder that involves multiple molecular pathways, making it a challenge for clinicians to identify effective therapies. Pulmonary artery smooth muscle cells (PASMCs) play a crucial role in HPH pathogenesis by proliferating, resisting apoptosis, and promoting vascular remodelling. Curcumin, a natural polyphenolic compound, has shown potential as a therapeutic agent for HPH by reducing pulmonary vascular resistance, inhibiting vascular remodelling, and promoting apoptosis of PASMCs. Regulation of PASMCs could significantly inhibits HPH. However, curcumin has the disadvantages of poor solubility and low bioavailability, and its derivative WZ35 has better biosafety. Here, Cu-based metal organic frameworks (MOFCu) was fabricated to encapsulate the curcumin analogue WZ35 (MOFCu@WZ35) for the inhibition of PASMCs proliferation. The authors found that the MOFCu@WZ35 could promote the death of PASMCs. Furthermore, the authors believed that this drug delivery system will effectively alleviate the HPH.
The present research aims to encapsulate lawsone in polylactic-co-glycolic acid (PLGA) nanoparticles modified with folic acid (FA) and chitosan (CS) to study its anticancer effects against Panc-1 cells. The nanoparticles were analysed in means of shape/size and zeta potential index using scanning electron microscope and dynamic light scattering. High-performance liquid chromatography was applied to evaluate the lawsone entrapment efficacy. The authors performed acridine orange/propidium iodide staining and flow cytometry to monitor apoptosis induction and cell cycle arrest. The expressions of apoptosis-related genes (BAX and BCL-2) were assessed by real time PCR. Nanoparticle antioxidative and antibacterial activities were examined by DPPH/ABTS scavenging assay, disk diffusion method, and minimum inhibitory concentration and minimum bactericidal concentration evaluation. The NPs were 229.65 nm, the encapsulation efficiency was 81%. The concentration of lawsone that exerts 50% cell growth inhibition (IC50) against Panc-1 cells was calculated 118.4 μL. Apoptosis induction was evidenced by the increased number of orange cells and increased proportion of cells in G1-Sub phase respectively. Moreover, lawsone-loaded nanoparticle upregulated BAX gene expression, while downregulated BCL2expression, suggesting the activation of apoptotic pathway. The observed cytotoxic/apoptotic properties suggest that Lawson-loaded PLGA-FA-CS-NPs hold a great potential in pancreatic cancer treatment.
The treatment of periodontitis focuses on controlling the progression of inflammation, reducing plaque accumulation, and promoting bone tissue reconstruction. Among them, the reconstruction of irregular bone resorption caused by periodontitis is a long-standing challenge. At present, the local drug treatment of periodontitis is mainly anti-inflammatory and antibacterial drugs. In this study, psoralen (Pso), a Chinese herbal medicine with anti-inflammatory, antibacterial, and osteogenic effects, was selected for the local treatment of periodontitis. Meanwhile, an injectable methacrylate gelatin (GelMA) platform loading with Pso was constructed. Pso-GelMA had the properties of fluidity, light cohesion, self-healing, and slow release, which could be better used in the deep and narrow structure of the periodontal pocket, and greatly increased the effectiveness of local drug delivery. The pore size of Gelma hydrogel did not change after loading Pso by SEM. In vitro, Pso-GelMA effectively upregulated the expression of osteogenic genes and proteins, increased alkaline phosphatase activity, promoted the mineralisation of rat bone marrow mesenchymal stem cells (BMSCs) extracellular matrix, and had significant antibacterial effects on Staphylococcus aureus and Fusobacterium nucleatum. Therefore, Pso-GelMA has immense promise in the adjuvant treatment of periodontitis.
Atherosclerosis is a progressive inflammatory disease characterised by excessive lipid accumulation and inflammatory cell infiltration and is the basis of most cardiovascular diseases and peripheral arterial diseases. Therefore, an effectively targeted delivery system is urgently needed to deliver ferroptosis-specific inhibitors to the site of arterial plaque and the inflammatory microenvironment. Inspired by the fact that neutrophils can be recruited to arterial plaques under the action of adhesion molecules and chemokines, the authors developed a neutrophil membrane hybrid liposome nano-mimetic system (Ptdser-NM-Lipo/Fer-1) that delivers Ferrostatin-1 (Fer-1) to the atherosclerotic plaque effectively, which is composed of Fer-1-loaded Ptdser-modified liposomes core and neutrophils shell. Fer-1 was released at the AS plaque site to remove reactive oxygen species (ROS) and improve the inflammatory microenvironment. In vitro ROS clearance experiments have shown that 50 μmol/ml Fer-1 can significantly remove ROS produced by H2O2-induced MOVAS cells and Ptdser-NM-Lipo/Fer-1 revealed a 3-fold increase in the inhibition rate of ROS than free Fer-1 in induced-RAW264.7, demonstrating its superior ROS-cleaning effect. Based on the interaction of adhesion molecules, such as vascular cell adhesion molecule 1, ICAM-1, P-selectin, E-selectin, and chemokines released in the inflamed site, the aorta in NM-Lipo-treated mice displayed 1.3-fold greater radiant efficiency than platelet membrane-Lipo-treated mice. Meanwhile, due to the modification of the Ptdser, the aorta in Ptdser-NM-Lipo/Fer-1-treated mice exhibited the highest fluorescence intensity, demonstrating its excellent targeting ability for atherosclerosis. Therefore, we present a specific formulation for the treatment of atherosclerosis with the potential for novel therapeutic uses.
Ellagic acid (EA), which is widely distributed in many foods, has been found to possess inhibitory activity against xanthine oxidase (XO). However, there is ongoing debate about the difference in XO inhibitory activity between EA and allopurinol. Additionally, the inhibitory kinetics and mechanism of EA on XO are still unclear. Herein, the authors systematically studied the inhibitory effects of EA on XO. The authors’ findings showed that EA is a reversible inhibitor with mixed-type inhibition, and its inhibitory activity is weaker than allopurinol. Fluorescence quenching experiments suggested that the generation of EA-XO complex was exothermic and spontaneous. In silico analysis further confirmed that EA entered the XO catalytic centre. Furthermore, the authors verified the anti-hyperuricemia effect of EA in vivo. This study elucidates the inhibition kinetics and mechanism of EA on XO, and lays a theoretical foundation for the further development of drugs and functional foods containing EA for the treatment of hyperuricemia.
About 50% of cancer patients receive radiation therapy. Despite the therapeutic benefits of this method, the toxicity of radiation in the normal tissues is unavoidable To improve the quality of radiation therapy, in addition to other methods such as IMRT, IGRT, and high radiation dose, nanoparticles have shown excellent potential when ionising radiation is applied to the target volume. Recently, bismuth-based nanoparticles (BiNPs) have become particularly popular in radiation therapy due to their high atomic numbers (Z), high X-ray attenuation coefficient, low toxicity, and low cost. Moreover, it is easy to synthesise in a variety of sizes and shapes. This study aimed to review the effects of the bismuth-based NP and its combination with other compounds, and their potential synergies in radiotherapy, discussed based on their physical, chemical, and biological interactions. Targeted and non-targeted bismuth-based NPs used in radiotherapy as radiosensitizers and dose enhancement effects are described. The results reported in the literature were categorised into various groups. Also, this review has highlighted the importance of bismuth-based NPs in different forms of cancer treatment to find the highest efficiency for applying them as a suitable candidate for various cancer therapy and future clinical applications.
The outbreak of COVID-19 disease, the cause of severe acute respiratory syndrome, is considered a worldwide public health concern. Although studies indicated that the virus could spread through respiratory particles or droplets in close contact, current research have revealed that the virus stays viable in aerosols for several hours. Numerous investigations have highlighted the protective role of air purifiers in the management of COVID-19 transmission, however, there are still some doubts regarding the efficiency and safety of these technologies. According to those observations, using a proper ventilation system can extensively decrease the spread of COVID-19. However, most of those strategies are currently in the experimental stages. This review aimed at summarising the safety and effectiveness of the recent approaches in this field including using nanofibres that prevent the spread of airborne viruses like SARS-CoV-2. Here, the efficacy of controlling COVID-19 by means of combining multiple strategies is comprehensively discussed.
To assess and evaluate Chitosan-Metamizole nanoparticles for fracture healing and analgesic potential, nanoparticles were formulated using the ionotropic gelation method. The nanoparticles were evaluated for particle size, zeta potential, polydispersity index, loading efficiency, surface characteristics and drug release properties. The analgesic activity was determined in carrageenan-induced arthritic male Wister rats. Further fracture healing potency, mechanical testing, radiographic examination and bone histology of the femur were studied. The drug loading efficiency of 11.38%–17.45%, particle size of 140–220 nm, and zeta potential of 19.12–23.14 mV were observed with a spherical, smooth appearance. Nanoparticles showed sustained release behaviour over a longer period. Nearly 4-fold inhibition of oedema was observed in animals treated with nanoparticles with excellent fracture healing potential. The femurs treated with nanoparticles required greater force to fracture. Nanoparticles significantly improved the strength and healing process. Histopathological studies showed the potential of nanoparticles in the healing process. The study confirmed the potential of nanoparticles in fracture healing and enhancement of analgesic activity.
Melanoma is a dangerous type of skin cancer sometimes treated with radiotherapy. However, it induces damage to the surrounding healthy tissue and possibly further away areas. Therefore, it is necessary to give a lower dose to the patient with targeted therapy. In this study, the radio-sensitising effect of gold-coated iron oxide nanoparticles on electron beam radiotherapy of a melanoma tumour with magnetic targeting in a mouse model was investigated. Gold-coated iron oxide nanoparticles were prepared in a steady procedure. The melanoma tumour model was induced in mice. Animals were divided into five groups: (1) normal; (2) melanoma; (3) gold-coated iron oxide nanoparticles alone; (4) electron beam radiotherapy; (5) electron beam radiotherapy plus gold-coated iron oxide nanoparticles. The magnet was placed on the tumour site for 2 h. The tumours were then exposed to 6 MeV electron beam radiotherapy for a dose of 8 Gy. Inductively coupled plasma optical emission spectrometry test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay blood test were also performed. Gold-coated iron oxide nanoparticles with magnetic targeting before electron beam radiotherapy reduced the growth of the tumour compared to the control group. Blood tests did not show any significant toxicity. Deposition of nanoparticles was more in the tumour and spleen tissue and to a lesser extent in the liver, kidney, and lung tissues. The synergistic effect of nanoparticles administered by the intraperitoneal route and then concentrated into the tumour area by application of an external permanent magnet, before delivery of the electron beam radiotherapy improved the overall cancer treatment outcome and prevented metal distribution side effects.
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