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1.
Sci Adv ; 10(19): eadm9561, 2024 May 10.
Article En | MEDLINE | ID: mdl-38718119

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 → •O2- and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.


Colorectal Neoplasms , Immunotherapy , Tumor Microenvironment , Colorectal Neoplasms/therapy , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Immunotherapy/methods , Animals , Mice , Humans , Catalysis , Cell Line, Tumor , Nanostructures/chemistry , Biomimetic Materials/chemistry , Administration, Oral , Titanium/chemistry , Biomimetics/methods , Lactic Acid/chemistry , Dendritic Cells/immunology , Dendritic Cells/metabolism , Barium Compounds
2.
Adv Sci (Weinh) ; : e2310211, 2024 Mar 09.
Article En | MEDLINE | ID: mdl-38460166

The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the blood-brain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2 O2 into O2 , not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.

3.
Osteoporos Int ; 35(6): 1049-1059, 2024 Jun.
Article En | MEDLINE | ID: mdl-38459138

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.


Bone Density , Cancellous Bone , Humerus , Tomography, X-Ray Computed , Humans , Bone Density/physiology , Male , Female , Middle Aged , Tomography, X-Ray Computed/methods , Aged , Reproducibility of Results , Humerus/diagnostic imaging , Humerus/physiology , Cancellous Bone/diagnostic imaging , Cancellous Bone/physiopathology , Cancellous Bone/physiology , Algorithms , Phantoms, Imaging , Adult , Osteoporosis/physiopathology , Osteoporosis/diagnostic imaging , Aged, 80 and over
5.
Inorg Chem ; 63(7): 3317-3326, 2024 Feb 19.
Article En | MEDLINE | ID: mdl-38329889

A new 3D zinc-based metal-organic framework {[Zn7L2(DMF)3(H2O)(OH)2]·5DMF}n (1) (H6L = 5,5',5″-(methylsilanetriyl) triisophthalic acid) was constructed with an organosilicon-based linker, where H6L is a tetrahedral structure furnished with rich -COO- chelating sites for Zn(II) immobilization. Compound 1 exhibited two types of irregular one-dimensional channels and a three-dimensional skeleton with large specific surface area, making it a promising catalytic platform. Moreover, by incorporation of the second metal ion into the inorganic node of framework 1, isomorphic bimetallic MOF ZnMg-1 was successfully synthesized. ZnMg-1 demonstrated enhanced catalytic activity compared to 1 under identical conditions. Contrast experiments and theoretical calculations indicate that bimetallic active sites play a facilitating role in the chemical fixation of epoxides and CO2. It indicated that efficient chemical fixation of CO2 to cyclic carbonates was obtained over isomorphic MOF catalysts 1 and ZnMg-1.

6.
Int J Biochem Cell Biol ; 169: 106539, 2024 Apr.
Article En | MEDLINE | ID: mdl-38290690

Doxorubicin (DOX), a widely used chemotherapy agent in cancer treatment, encounters limitations in clinical efficacy due to associated cardiotoxicity. This study aims to explore the role of AKT serine/threonine kinase 2 (AKT2) in mitigating DOX-induced oxidative stress within the heart through both intracellular and extracellular signaling pathways. Utilizing Akt2 knockout (KO) and Nrf2 KO murine models, alongside neonatal rat cardiomyocytes (NRCMs), we systematically investigate the impact of AKT2 deficiency on DOX-induced cardiac injury. Our findings reveal that DOX administration induces significant oxidative stress, a primary contributor to cardiac injury. Importantly, Akt2 deficiency exhibits a protective effect by alleviating DOX-induced oxidative stress. Mechanistically, Akt2 deficiency facilitates nuclear translocation of NRF2, thereby suppressing intracellular oxidative stress by promoting the expression of antioxidant genes. Furthermore, We also observed that AKT2 inhibition facilitates superoxide dismutase 2 (SOD2) expression both inside macrophages and SOD2 secretion to the extracellular matrix, which is involved in lowering oxidative stress in cardiomyocytes upon DOX stimulation. The present study underscores the important role of AKT2 in mitigating DOX-induced oxidative stress through both intracellular and extracellular signaling pathways. Additionally, our findings propose promising therapeutic strategies for addressing DOX-induced cardiomyopathy in clinic.


Myocytes, Cardiac , NF-E2-Related Factor 2 , Rats , Mice , Animals , Myocytes, Cardiac/metabolism , NF-E2-Related Factor 2/metabolism , Doxorubicin/adverse effects , Oxidative Stress , Cardiotoxicity/drug therapy , Cardiotoxicity/metabolism , Apoptosis
7.
Life Sci ; 341: 122474, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38296191

AIMS: This work sought to investigate the mechanism underlying the STING signaling pathway during myocardial infarction (MI), and explore the involvement and the role of SIRT6 in the process. MAIN METHODS: Mice underwent the surgery of permanent left anterior descending (LAD) artery constriction. Primary cardiomyocytes (CMs) and fibroblasts were subjected to hypoxia to mimic MI in vitro. STING expression was assessed in the infarct heart, and the effect of STING inhibition on cardiac fibrosis was explored. This study also evaluated the regulatory effect of STING by SIRT6 in macrophages. KEY FINDINGS: STING protein was increased in the infarct heart tissue, highlighting its involvement in the post-MI inflammatory response. Hypoxia-induced death of CMs and fibroblasts contributed to the upregulation of STING in macrophages, establishing the involvement of STING in the intercellular signaling during MI. Inhibition of STING resulted in a significant reduction of cardiac fibrosis at day 14 after MI. Additionally, this study identified SIRT6 as a key regulator of STING via influencing its acetylation and ubiquitination in macrophages, providing novel insights into the posttranscriptional modification and expression of STING at the acute phase after myocardial infarction. SIGNIFICANCE: This work shows the key role of SIRT6/STING signaling in the pathogenesis of cardiac injury after MI, suggesting that targeting this regulatory pathway could be a promising strategy to attenuate cardiac fibrosis after MI.


Heart Injuries , Myocardial Infarction , Sirtuins , Animals , Mice , Disease Models, Animal , Fibrosis , Heart Injuries/metabolism , Hypoxia/metabolism , Macrophages/metabolism , Mice, Inbred C57BL , Myocardial Infarction/metabolism , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Signal Transduction , Sirtuins/metabolism
8.
Water Res ; 250: 121064, 2024 Feb 15.
Article En | MEDLINE | ID: mdl-38154336

Microplastics (MPs) have emerged as a novel and highly concerning contaminant that is ubiquitous in the aqueous environment. However, the aging of MPs induced by dissolved organic matter (DOM), especially biochar-derived dissolved organic matter (BDOM), and the biological toxicity after aging are not fully understood. In this study, the effects of biochar-derived BDOMs on the photoaging and biotoxicity of MPs were investigated at different pyrolysis temperatures using micro-scale polyethylene (PE) as an example. The results showed that the amount of ·OH generated by the BDOM/PE systems was related to the molecular composition and structure of BDOMs. High temperature BDOM7/9 with less lignin-like (34.33 % / 41.80 %) and more lipid (24.58 % / 19.88 %) content could produce more ·OH by itself, and its binding ability with PE was weaker due to its less hydrophobic components (SUVA260 = 0.10 / 0.11), which resulted in a weaker shading effect and less inhibition of the system, thus resulting in more ·OH production in the high temperature BDOM7/9/PE system. However, the involvement of BDOM, although favoring the long-term stable ·OH production of the system, did not significantly promote the photoaging of MPs. Furthermore, combined in vivo and in vitro biotoxicity studies of MPs showed that photoaging PE with the involvement of BDOM greatly improved systemic inflammation and tissue damage, as well as reactive oxygen species (ROS, such as ·OH and -OH)-induced cell death. For example, the addition of BDOM5/PE-light reduced the cell death of human lung, liver, and kidney cells from 54.70 %, 69.39 %, and 48.35 % to 22.78 %, 33.13 %, and 25.83 %, respectively, compared to the PE-light group. The results of this study contribute to an in-depth understanding of the environmental behavior of BDOM and MPs systems.


Charcoal , Dissolved Organic Matter , Microplastics , Humans , Microplastics/toxicity , Plastics , Temperature , Pyrolysis , Polyethylene , Aging
9.
Life Sci ; 338: 122386, 2024 Feb 01.
Article En | MEDLINE | ID: mdl-38159594

Diabetic retinopathy is a complex and progressive ocular complication of diabetes mellitus and is a leading cause of blindness in people of working age worldwide. The pathophysiology of diabetic retinopathy involves multifactorial processes, including oxidative stress, inflammation and vascular abnormalities. Understanding the underlying molecular mechanisms involved in its pathogenesis is essential for the development of effective therapeutic interventions. One of the pathways receiving increasing attention is the Keap1-Nrf2 signaling pathway, which regulates the cellular response to oxidative stress by activating Nrf2. In this review, we analyze the current evidence linking Keap1-Nrf2 signaling pathway dysregulation to diabetic retinopathy. In addition, we explore the potential therapeutic implications and the challenges of targeting this pathway for disease management. A comprehensive understanding of the molecular mechanisms of diabetic retinopathy and the therapeutic potential of the Keap1-Nrf2 pathway may pave the way for innovative and effective interventions to combat this vision-threatening disease.


Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/therapy , Diabetic Retinopathy/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Signal Transduction
10.
Mater Today Bio ; 23: 100834, 2023 Dec.
Article En | MEDLINE | ID: mdl-38024841

Achieving precision treatment in bone tissue engineering (BTE) remains a challenge. Photothermal therapy (PTT), as a form of precision therapy, has been extensively investigated for its safety and efficacy. It has demonstrated significant potential in the treatment of orthopedic diseases such as bone tumors, postoperative infections and osteoarthritis. However, the high temperatures associated with PTT can lead to certain limitations and drawbacks. In recent years, researchers have explored the use of biomaterials for mild photothermal therapy (MPT), which offers a promising approach for addressing these limitations. This review provides a comprehensive overview of the mechanisms underlying MPT and presents a compilation of photothermal agents and their utilization strategies for bone tissue repair. Additionally, the paper discusses the future prospects of MPT-assisted bone tissue regeneration, aiming to provide insights and recommendations for optimizing material design in this field.

11.
Nanoscale ; 15(48): 19407-19422, 2023 Dec 14.
Article En | MEDLINE | ID: mdl-37965689

Treating cancer remains one of the most formidable challenges in modern medicine, with traditional treatment options often being limited by poor therapeutic outcomes and unacceptable side effects. Nanocatalytic therapy activates tumor-localized catalytic reactions in situ via nontoxic or minimally toxic nanocatalysts responding to unique cues from the tumor microenvironment or external stimuli. In particular, sonocatalytic cancer therapy is a promising approach that has emerged as a potential solution to this problem through the combination of ultrasound waves and catalytic materials to selectively target and destroy cancer cells. Compared to light, ultrasound exhibits higher spatial precision, lower energy attenuation, and superior tissue penetrability, furnishing more energy to catalysts. Multidimensional modulation of nanocatalyst structures and properties is pivotal to maximizing catalytic efficiency given constraints in external stimulative energy as well as substrate types and levels. In this review, we discuss the various theories and mechanisms underlying sonocatalytic cancer therapy, as well as advanced catalysts that have been developed for this application. Additionally, we explore the design of sonocatalytic cancer therapy systems, including the use of heterojunction catalysts and the optimal conditions for achieving maximum therapeutic effects. Finally, we highlight the potential benefits of sonocatalytic cancer therapy over traditional cancer treatments, including its noninvasive nature and lower toxicity.


Neoplasms , Humans , Neoplasms/therapy , Ultrasonic Waves , Tumor Microenvironment
12.
Life Sci ; 333: 122187, 2023 Nov 15.
Article En | MEDLINE | ID: mdl-37858715

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired glucose homeostasis. Oxidative stress, arising from an imbalance between reactive oxygen species (ROS) production and antioxidant defense systems, plays a significant role in the development and progression of T2DM. The sirtuin family, particularly Sirt1, Sirt3, and Sirt6, have emerged as key regulators of oxidative stress in various cellular processes. This review aims to explore the role of the sirtuin family in oxidative stress during the progression of T2DM and their potential as therapeutic targets. We discussed the mechanisms through which sirtuins modulate oxidative stress, their impact on insulin sensitivity, and beta-cell function involved in T2DM. Furthermore, we highlight drugs targeting sirtuin activation and related complications in T2DM. This review summarizes the role as well as mechanism of sirtuins in the regulation of oxidative stress in T2DM and available drugs targeting sirtuins in clinic, which may provide novel insights into the mechanism and therapy of T2DM.


Diabetes Mellitus, Type 2 , Sirtuin 3 , Sirtuins , Humans , Sirtuins/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Oxidative Stress , Sirtuin 3/metabolism , Antioxidants/metabolism
13.
Pulm Pharmacol Ther ; 83: 102259, 2023 Dec.
Article En | MEDLINE | ID: mdl-37726074

BACKGROUND: Acute pneumonia induced by Pseudomonas aeruginosa is characterized by massive infiltration of inflammatory cell and the production of reactive oxygen species (ROS), which lead to severe and transient pulmonary inflammation and acute lung injury. However, P.aeruginosa infection is resistant to multiple antibiotics and causes high mortality in clinic, the search for alternative prophylactic and therapeutic strategies is imperative. PURPOSE: This study was aimed to investigate the anti-inflammatory and antioxidant effects of DMB, a novel derivative of berberine, and explore the role of AIM2 inflammasome in P. aeruginosa-induced acute pneumonia. METHODS: Acute pneumonia mice were established by tracheal injection of P. aeruginosa suspension. Pathological changes of lung tissue were observed by its appearance and H&E staining. The lung coefficient ratio was measured to evaluate pulmonary edema. Inflammatory factors were detected by qRT-PCR, western blotting and immunohistochemistry. ROS and other indicators of oxidative damage were analyzed by flow cytometry and specific kit. Proteins related to AIM2 inflammasome were detected by western blotting. RESULTS: Compared with the P. aeruginosa-induced group, DMB ameliorated pulmonary edema, hyperemia, and pathological damage based on its appearance and H&E staining in DMB groups. First, DMB attenuated the inflammatory response induced by P.aeruginosa. Compared with the P. aeruginosa-induced group, the lung coefficient ratio was decreased by 31.5%, the MPO activity of lung tissue was decreased by 44.0%, the mRNA expression levels of TNF-α, IL-1ß and IL-6 were decreased by 64.8%, 51.2% and 64.0% respectively, and those protein expression levels were decreased by 40.1%, 42.8% and 47.8% respectively, and the number of white blood cells, neutrophils and monocytes were decreased by 53.5%, 29.4% and 13.7% in high dose (200 mg/kg) DMB group. Second, DMB alleviates oxidative stress in the lung tissue during P. aeruginosa-induced acute pneumonia. Compared with the P. aeruginosa-induced group, the level of GSH was increased by 42.5% and MDA was decreased by 49.5% in high dose DMB group. Moreover, the western blotting results showed that DMB markedly suppressed the expression of AIM2, ASC, Cleaved caspase1 and decreased the secretion of IL-1ß. Additionally, these results were also confirmed by in vitro experiments using MH-S and BEAS-2B cell lines. CONCLUSIONS: Taken together, these results indicated that DMB ameliorates P. aeruginosa-induced acute pneumonia through anti-inflammatory, antioxidant effects, and inhibition of AIM2 inflammasome activation.


Pneumonia , Pulmonary Edema , Animals , Mice , Inflammasomes/adverse effects , Inflammasomes/metabolism , Pseudomonas aeruginosa , Reactive Oxygen Species/metabolism , Antioxidants/pharmacology , Antioxidants/metabolism , Pulmonary Edema/drug therapy , Pneumonia/drug therapy , Pneumonia/chemically induced , Oxidative Stress , Anti-Inflammatory Agents/adverse effects
14.
Nat Commun ; 14(1): 5140, 2023 08 23.
Article En | MEDLINE | ID: mdl-37612298

The exogenous excitation requirement and electron-hole recombination are the key elements limiting the application of catalytic therapies. Here a tumor microenvironment (TME)-specific self-triggered thermoelectric nanoheterojunction (Bi0.5Sb1.5Te3/CaO2 nanosheets, BST/CaO2 NSs) with self-built-in electric field facilitated charge separation is fabricated. Upon exposure to TME, the CaO2 coating undergoes rapid hydrolysis, releasing Ca2+, H2O2, and heat. The resulting temperature difference on the BST NSs initiates a thermoelectric effect, driving reactive oxygen species production. H2O2 not only serves as a substrate supplement for ROS generation but also dysregulates Ca2+ channels, preventing Ca2+ efflux. This further exacerbates calcium overload-mediated therapy. Additionally, Ca2+ promotes DC maturation and tumor antigen presentation, facilitating immunotherapy. It is worth noting that the CaO2 NP coating hydrolyzes very slowly in normal cells, releasing Ca2+ and O2 without causing any adverse effects. Tumor-specific self-triggered thermoelectric nanoheterojunction combined catalytic therapy, ion interference therapy, and immunotherapy exhibit excellent antitumor performance in female mice.


Hydrogen Peroxide , Neoplasms , Female , Animals , Mice , Immunotherapy , Neoplasms/therapy , Antigen Presentation , Biological Transport , Tumor Microenvironment
15.
Anal Chem ; 95(29): 11061-11069, 2023 07 25.
Article En | MEDLINE | ID: mdl-37439625

The simultaneous quantification of multiple microRNAs (miRNA) in a single cell can help scientists understand the relationship between different miRNA groups and different types of cancers from an miRNA omics perspective at the single-cell level. However, there currently remains a challenge in developing techniques for the simultaneous absolute quantification of multiple miRNAs in single cells. Herein, we propose a framework nucleic acid (FNA)-mediated multimodal tandem multivariate signal amplification strategy for simultaneous absolute quantification of three different miRNAs in a single cell. In this study, DNA hexahedron FNAs (DHFs) and DNA tetrahedron FNAs (DTFs) were first prepared, multiple DNA hairpins and substrates were then connected to the hexahedron frame nucleic acid as the target recognition units, and three substrates with labeled FAM fluorophores on the tetrahedral frame nucleic acid served as signal output units. After the two types of FNAs entered the cell, they reacted with three different miRNAs (miRNA-155, miRNA-373, and miRNA-21) and multimodal tandem multivariate signal amplification was initiated simultaneously, reducing the detection limit of the three miRNAs to 8 × 10-15, 2 × 10-15, and 1 × 10-15 M, respectively. The detection sensitivity of the three miRNAs was simultaneously increased by six orders of magnitude, reaching the quantitative requirement of trace miRNAs in single cells. Combined with single-cell injection, membrane melting, and intracellular component separation technology on a microchip electrophoresis platform, we achieved the simultaneous absolute quantification of three different miRNAs in a single cell, thereby providing an important novel method that can be used to conduct single-cell research.


MicroRNAs , Nucleic Acids , MicroRNAs/analysis , DNA/genetics , Fluorescent Dyes , Nucleic Acid Amplification Techniques/methods
16.
Opt Express ; 31(11): 17836-17847, 2023 May 22.
Article En | MEDLINE | ID: mdl-37381507

Understanding the formation mechanisms of the nanostructures and their designs has important implications for both the fundamental science and application prospects. In this study, we proposed a strategy for femtosecond laser-induced high regularity concentric rings within silicon microcavity. The morphology of the concentric rings can be flexibly modulated by the pre-fabricated structures and the laser parameters. The physics involved is deeply explored by the Finite-Difference-Time-Domain simulations, which reveals that the formation mechanism can be attributed to the near-field interference of the incident laser and the scattering light from the pre-fabricated structures. Our results provide a new method for creating the designable periodic surface structures.

17.
Front Immunol ; 14: 1130404, 2023.
Article En | MEDLINE | ID: mdl-37168866

Introduction: The colitis induced by trinitrobenzenesulfonic acid (TNBS) is a chronic and systemic inflammatory disease that leads to intestinal barrier dysfunction and autoimmunedisorders. However, the existing treatments of colitis are associated with poor outcomes, and the current strategies remain deep and long-time remission and the prevention of complications. Recently, demethyleneberberine (DMB) has been reported to be a potential candidate for the treatment of inflammatory response that relied on multiple pharmacological activities, including anti-oxidation and antiinflammation. However, the target and potential mechanism of DMB in inflammatory response have not been fully elucidated. Methods: This study employed a TNBS-induced colitis model and acute sepsis mice to screen and identify the potential targets and molecular mechanisms of DMB in vitro and in vivo. The purity and structure of DMB were quantitatively analyzed by high-performance liquid chromatography (HPLC), mass spectrometry (MS), Hydrogen nuclear magnetic resonance spectroscopy (1H-NMR), and infrared spectroscopy (IR), respectively. The rats were induced by a rubber hose inserted approximately 8 cm through their anus to be injected with TNBS. Acute sepsis was induced by injection with LPS via the tail vein for 60 h. These animals with inflammation were orally administrated with DMB, berberine (BBR), or curcumin (Curc), respectively. The eukaryotic and prokaryotic expression system of myeloid differentiation protein-2 (MD-2) and its mutants were used to evaluate the target of DMB in inflammatory response. Resluts: DMB had two free phenolic hydroxyl groups, and the purity exceeded 99% in HPLC. DMB alleviated colitis and suppressed the activation of TLR4 signaling in TNBS-induced colitis rats and LPS-induced RAW264.7 cells. DMB significantly blocked TLR4 signaling in both an MyD88-dependent and an MyD88-independent manner by embedding into the hydrophobic pocket of the MD-2 protein with non-covalent bonding to phenylalanine at position 76 in a pi-pi T-shaped interaction. DMB rescued mice from sepsis shock induced by LPS through targeting the TLR4-MD-2 complex. Conclusion: Taken together, DMB is a promising inhibitor of the MD-2 protein to suppress the hyperactivated TLR4 signaling in inflammatory response.


Colitis , Toll-Like Receptor 4 , Rats , Mice , Animals , Toll-Like Receptor 4/metabolism , NF-kappa B/metabolism , Myeloid Differentiation Factor 88/metabolism , Lipopolysaccharides/toxicity , Lymphocyte Antigen 96 , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism
18.
Front Cell Infect Microbiol ; 13: 1142029, 2023.
Article En | MEDLINE | ID: mdl-37033476

Fungal diseases have posed a great challenge to global health, but have fewer solutions compared to bacterial and viral infections. Development and application of new treatment modalities for fungi are limited by their inherent essential properties as eukaryotes. The microorganism identification and drug sensitivity analyze are limited by their proliferation rates. Moreover, there are currently no vaccines for prevention. Polymer science and related interdisciplinary technologies have revolutionized the field of fungal disease management. To date, numerous advanced polymer-based systems have been developed for management of fungal diseases, including prevention, diagnosis, treatment and monitoring. In this review, we provide an overview of current needs and advances in polymer-based strategies against fungal diseases. We high light various treatment modalities. Delivery systems of antifungal drugs, systems based on polymers' innate antifungal activities, and photodynamic therapies each follow their own mechanisms and unique design clues. We also discuss various prevention strategies including immunization and antifungal medical devices, and further describe point-of-care testing platforms as futuristic diagnostic and monitoring tools. The broad application of polymer-based strategies for both public and personal health management is prospected and integrated systems have become a promising direction. However, there is a gap between experimental studies and clinical translation. In future, well-designed in vivo trials should be conducted to reveal the underlying mechanisms and explore the efficacy as well as biosafety of polymer-based products.


Antifungal Agents , Mycoses , Humans , Antifungal Agents/therapeutic use , Polymers/therapeutic use , Mycoses/diagnosis , Mycoses/drug therapy , Mycoses/prevention & control , Fungi
19.
Biomater Adv ; 149: 213394, 2023 Jun.
Article En | MEDLINE | ID: mdl-37001309

Infection prevention and bone-implant integration remain major clinical challenges. Silver nanoparticle (AgNPs) bone-implant coatings have received extensive attention. Balancing the toxicity and antibacterial properties of AgNP coatings has become a significant problem. In this study, inspired by the structure of the ant-nest, a polyetherimide (PEI) coating with ant-nest structure was prepared, aiming to realize the structural modification of the AgNPs coating. AgNPs were loaded in the inner porous area of the PEI ant-nest coating, avoiding direct contact between AgNPs and cells. The nanopores on the surface of the coating ensured the orderly release of silver ions. SEM, FTIR, XPS, and XRD experiments confirmed that the PEI ant-nest coating was successfully prepared. Interestingly, in the PEI ant-nest coating, Ag+ showed a steady increase in the release trend within 28 days, and there was no early burst release phenomenon. In -vivo experiments showed a good control effect for local infection. In order to improve the osteogenic properties of the materials, 45S5 bioactive glasses (BG) were loaded to achieve further osseointegration. In general, this natural ant-nest-inspired surface modification coating for orthopedic prostheses provides a new strategy for balancing the antibacterial and toxic effects of AgNP coatings.


Ants , Artificial Limbs , Metal Nanoparticles , Animals , Silver/pharmacology , Biomimetics , Osseointegration , Anti-Bacterial Agents/pharmacology
20.
Am J Transl Res ; 15(2): 1223-1230, 2023.
Article En | MEDLINE | ID: mdl-36915791

OBJECTIVE: To construct a model to predict the risk of gestational diabetes mellitus (GDM) based on a nomogram and verify it. METHODS: Data from 182 patients with GDM treated in Xi'an International Medical Center Hospital from January 2018 to May 2021 were retrospectively analyzed. A total of 491 normal parturients who underwent physical examination in Xi'an International Medical Center Hospital during the same period were selected as controls. With a ratio of 7:3, patients with GDM were divided into a training group (n=128) and a verification (n=54) group, and 491 normal parturients were divided into a training control group (n=344) and a verification control group (n=147). Clinical data were collected, and risk factors for GDM were analyzed by logistic regression. R language was used to construct a prognostic prediction nomogram model for GDM, and a receiver operating characteristic curve was employed to evaluate the accuracy of this nomogram model in predicting the prognosis of GDM. RESULTS: Univariate analysis revealed that age, body mass index (BMI), family history of diabetes, hemoglobin, triglycerides, serum ferritin, and fasting blood glucose in the first trimester were different between the training group and the training control group (P<0.05). Multivariate analysis revealed that age, BMI, hemoglobin, triglycerides, serum ferritin, and fasting blood glucose in the first trimester were independent risk factors for GDM (P<0.05). Based on a logistic regression equation, the risk formula was -5.971 + 1.054 * age + 1.133 * BMI + 1.763 * hemoglobin + 1.260 * triglycerides + 3.041 * serum ferritin + 1.756 * fasting blood glucose in the first trimester. The area under the curve for predicting the risk of GDM in the training group was 0.920, and that of the validation group was 0.753. CONCLUSION: Age, BMI, hemoglobin, serum ferritin, and fasting blood glucose in the first trimester are risk factors for GDM.

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