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1.
J Colloid Interface Sci ; 671: 751-769, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38824748

ABSTRACT

Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.


Subject(s)
Anti-Bacterial Agents , Antineoplastic Agents , Catechin , Copper , Nanocomposites , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Copper/chemistry , Copper/pharmacology , Nanocomposites/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Animals , Mice , Humans , Catechin/chemistry , Catechin/pharmacology , Catechin/analogs & derivatives , Microbial Sensitivity Tests , Drug Resistance, Bacterial/drug effects , Photochemotherapy , Wound Infection/drug therapy , Wound Infection/pathology , Wound Infection/microbiology , Drug Screening Assays, Antitumor , Staphylococcus aureus/drug effects , Photothermal Therapy , Particle Size , Escherichia coli/drug effects , Cell Survival/drug effects , Cell Line, Tumor , Surface Properties , Cell Proliferation/drug effects
2.
Int J Nanomedicine ; 19: 5511-5522, 2024.
Article in English | MEDLINE | ID: mdl-38895144

ABSTRACT

Introduction: Chrysin has a wide range of biological activities, but its poor bioavailability greatly limits its use. Here, we attempted to prepare casein (cas)-based nanoparticles to promote the biotransfer of chrysin, which demonstrated better bioavailability and anti-infection activity compared to free chrysin. Methods: Cas-based chrysin nanoparticles were prepared and characterized, and most of the preparation process was optimized. Then, the in vitro and in vivo release characteristics were studied, and anti-pulmonary infection activity was evaluated. Results: The constructed chrysin-cas nanoparticles exhibited nearly spherical morphology with particle size and ζ potential of 225.3 nm and -33 mV, respectively. These nanoparticles showed high encapsulation efficiency and drug-loading capacity of 79.84% ± 1.81% and 11.56% ± 0.28%, respectively. In vitro release studies highlighted a significant improvement in the release profile of the chrysin-cas nanoparticles (CCPs). In vivo experiments revealed that the relative oral bioavailability of CCPs was approximately 2.01 times higher than that of the free chrysin suspension. Further investigations indicated that CCPs effectively attenuated pulmonary infections caused by Acinetobacter baumannii by mitigating oxidative stress and reducing pro-inflammatory cytokines levels, and the efficacy was better than that of the free chrysin suspension. Conclusion: The findings underscore the advantageous bioavailability of CCPs and their protective effects against pulmonary infections. Such advancements position CCPs as a promising pharmaceutical agent and candidate for future therapeutic drug innovations.


Subject(s)
Biological Availability , Caseins , Flavonoids , Nanoparticles , Particle Size , Flavonoids/chemistry , Flavonoids/pharmacology , Flavonoids/pharmacokinetics , Caseins/chemistry , Caseins/pharmacokinetics , Animals , Nanoparticles/chemistry , Mice , Drug Liberation , Male , Oxidative Stress/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Cytokines/metabolism , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics
3.
Colloids Surf B Biointerfaces ; 239: 113911, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38714079

ABSTRACT

An innovative nanozyme, iron-doped polydopamine (Fe-PDA), which integrates iron ions into a PDA matrix, conferred peroxidase-mimetic activity and achieved a substantial photothermal conversion efficiency of 43.5 %. Fe-PDA mediated the catalysis of H2O2 to produce toxic hydroxyl radicals (•OH), thereby facilitating lipid peroxidation in tumour cells and inducing ferroptosis. Downregulation of solute carrier family 7 no. 11 (SLC7A11) and solute carrier family 3 no. 2 (SLC3A2) in System Xc- resulted in decreased intracellular glutathione (GSH) production and inactivation of the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) pathway, contributing to ferroptosis. Moreover, the application of photothermal therapy (PTT) enhanced the effectiveness of chemodynamic therapy (CDT), accelerating the Fenton reaction for targeted tumour eradication while sparing adjacent non-cancerous tissues. In vivo experiments revealed that Fe-PDA significantly hampered tumour progression in mice, emphasizing the potential of the dual-modality treatment combining CDT and PTT for future clinical oncology applications.


Subject(s)
Ferroptosis , Indoles , Iron , Liver Neoplasms , Photothermal Therapy , Polymers , Indoles/chemistry , Indoles/pharmacology , Ferroptosis/drug effects , Polymers/chemistry , Polymers/pharmacology , Animals , Humans , Iron/chemistry , Iron/pharmacology , Mice , Liver Neoplasms/drug therapy , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Mice, Inbred BALB C , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/metabolism , Nanoparticles/chemistry , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Particle Size , Drug Screening Assays, Antitumor , Surface Properties
4.
Small ; : e2402073, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38686676

ABSTRACT

Natural polyphenolic compound rosmarinic acid (RA) has good antitumor activity. However, the distinctive tumor microenvironment, characterized by low pH and elevated levels of glutathione (GSH), enhances the tolerance of tumors to the singular anti-tumor treatment mode using RA, resulting in unsatisfactory therapeutic efficacy. Targeting nonapoptotic programmed cell death processes may provide another impetus to inhibit tumor growth. RA possesses the capability to coordinate with metal elements. To solve the effect restriction of the above single treatment mode, it is proposed to construct a self-assembled nanocomposite, Fe-RA. Under tumor microenvironment, Fe-RA nanocomposite exerts the characteristics of POD-like enzyme activity and depletion of GSH, producing a large amount of hydroxyl radical (·OH) while disrupting the antioxidant defense system of tumor cells. Moreover, due to the enhanced permeability and retention effect (EPR), Fe-RA can transport Fe2+ to a greater extent to tumor cells and increase intracellular iron content. Causing an imbalance in iron metabolism in tumor cells and promoting cell ferroptosis. The results of the synchrotron X-ray absorption spectroscopy (XAS) and high-resolution mass spectrometry (HRMS) prove the successful complexation of Fe-RA nanocomposite. Density functional theory (DFT) explains the efficient catalytic mechanism of its peroxide-like enzyme activity and the reaction principle with GSH.

5.
J Hazard Mater ; 470: 134245, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38603910

ABSTRACT

This study delved into the physiological and molecular mechanisms underlying the mitigation of cadmium (Cd) stress in the model medicinal plant Salvia miltiorrhiza through the application of ZnO quantum dots (ZnO QDs, 3.84 nm). A pot experiment was conducted, wherein S. miltiorrhiza was subjected to Cd stress for six weeks with foliar application of 100 mg/L ZnO QDs. Physiological analyses demonstrated that compared to Cd stress alone, ZnO QDs improved biomass, reduced Cd accumulation, increased the content of photosynthetic pigments (chlorophyll and carotenoids), and enhanced the levels of essential nutrient elements (Ca, Mn, and Cu) under Cd stress. Furthermore, ZnO QDs significantly lowered Cd-induced reactive oxygen species (ROS) content, including H2O2, O2-, and MDA, while enhancing the activity of antioxidant enzymes (SOD, POD, APX, and GSH-PX). Additionally, ZnO QDs promoted the biosynthesis of primary and secondary metabolites, such as total protein, soluble sugars, terpenoids, and phenols, thereby mitigating Cd stress in S. miltiorrhiza. At the molecular level, ZnO QDs were found to activate the expression of stress signal transduction-related genes, subsequently regulating the expression of downstream target genes associated with metal transport, cell wall synthesis, and secondary metabolite synthesis via transcription factors. This activation mechanism contributed to enhancing Cd tolerance in S. miltiorrhiza. In summary, these findings shed light on the mechanisms underlying the mitigation of Cd stress by ZnO QDs, offering a potential nanomaterial-based strategy for enhancing Cd tolerance in medicinal plants.


Subject(s)
Cadmium , Quantum Dots , Reactive Oxygen Species , Salvia miltiorrhiza , Zinc Oxide , Quantum Dots/chemistry , Zinc Oxide/chemistry , Zinc Oxide/toxicity , Salvia miltiorrhiza/drug effects , Salvia miltiorrhiza/metabolism , Cadmium/toxicity , Reactive Oxygen Species/metabolism , Stress, Physiological/drug effects , Antioxidants/metabolism , Gene Expression Regulation, Plant/drug effects
6.
J Biomater Sci Polym Ed ; 35(10): 1571-1583, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38613795

ABSTRACT

Nanometer zinc oxide (ZnONPs) offers strong antibacterial, wound healing, hemostatic benefits, and UV protection. Additionally, poly(hexamethylene biguanide)hydrochloride (PHMB) is an environmentally friendly polymer with strong bactericidal properties. However, the synergistic effect of the combination of ZnONPs and PHMB has not been previously explored. The purpose of this study is to explore the synergies of ZnONPs and PHMB and the healing efficacy of ZnO NPs-PHMB-hydrogel on skin wounds in mice infected with Staphylococcus aureus. Therefore, the mice were subjected to skin trauma to create a wound model and were subsequently infected with S. aureus, and then divided into various experimental groups. The repair effect was evaluated by assessing the healing rate, as well as measuring the levels of TNF-α, IL-2, EGF, and TGF-ß1 contents in the tissue. On the 4th and 9th days post-modeling, the Z-P group exhibited notably higher healing rates compared to the control group. However, on the 15th day, both the Z-P and AC groups achieved healing rates exceeding 99%. ZnO NPs-PHMB-hydrogel promoted the formation of a fully restored epithelium, increased new hair follicles and sebaceous glands beneath the epidermis, and markedly reduced inflammatory cell infiltration, which was markedly distinct from the control group. On the 7th day, the Z-P group exhibited significantly higher levels of EGF and TGF-ß1, along with a considerable reduction in the TNF-α levels as compared with the control group. These results affirmed that ZnO NPs-PHMB-hydrogel effectively inhibits S. aureus infection and accelerates skin wound healing.


Subject(s)
Anti-Bacterial Agents , Biguanides , Hydrogels , Staphylococcus aureus , Wound Healing , Zinc Oxide , Animals , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Biguanides/pharmacology , Biguanides/chemistry , Staphylococcus aureus/drug effects , Mice , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Skin/drug effects , Skin/microbiology , Skin/pathology , Staphylococcal Infections/drug therapy , Wound Infection/drug therapy , Wound Infection/microbiology , Male , Staphylococcal Skin Infections/drug therapy
7.
Theranostics ; 14(5): 1939-1955, 2024.
Article in English | MEDLINE | ID: mdl-38505601

ABSTRACT

Rationale: Cancer continues to be a significant public health issue. Traditional treatments such as surgery, radiotherapy, and chemotherapy often fall short because of intrinsic issues such as lack of specificity and poor drug delivery, leading to insufficient drug concentration at the tumor site and/or potential side effects. Consequently, improving the delivery of conventional chemotherapy drugs like doxorubicin (DOX) is crucial for their therapeutic efficacy. Successful cancer treatment is achieved when regulated cell death (RCD) of cancer cells, which includes apoptotic and non-apoptotic processes such as ferroptosis, is fundamental to successful cancer treatment. The developing field of nanozymes holds considerable promise for innovative cancer treatment approaches. Methods: A dual-metallic nanozyme system encapsulated with DOX was created, derived from metal-organic frameworks (MOFs), designed to combat tumors by depleting glutathione (GSH) and concurrently liberating DOX. The initial phase of the study examined the GSH oxidase-mimicking function of the dimetallic nanozyme (ZIF-8/SrSe) through enzyme kinetic assays and Density Functional Theory (DFT) simulations. Following this, we probed the ability of ZIF-8/SrSe@DOX to release DOX in response to the tumor microenvironment in vitro, alongside examining its anticancer capabilities and mechanisms prompting apoptosis or ferroptosis in cancer cells. Moreover, we established tumor-bearing animal models to corroborate the anti-tumor effectiveness of our nanozyme complex and to identify the involved apoptotic and ferroptotic pathways implicated. Results: Enzyme kinetic analyses demonstrated that the ZIF-8/SrSe nanozyme exhibits substantial GSH oxidase-like activity, effectively oxidizing reduced GSH to glutathione disulfide (GSSG), while also inhibiting glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). This inhibition led to an imbalance in iron homeostasis, pronounced caspase activation, and subsequent induction of apoptosis and ferroptosis in tumor cells. Additionally, the ZIF-8/SrSe@DOX nanoparticles efficiently delivered DOX, causing DNA damage and further promoting apoptotic and ferroptotic pathways. Conclusions: This research outlines the design of a novel platform that combines chemotherapeutic agents with a Fenton reaction catalyst, offering a promising strategy for cancer therapy that leverages the synergistic effects of apoptosis and ferroptosis.


Subject(s)
Ferroptosis , Neoplasms , Regulated Cell Death , Animals , Apoptosis , Drug Delivery Systems , Glutathione , Glutathione Disulfide , Doxorubicin/pharmacology , Oxidoreductases , Cell Line, Tumor , Neoplasms/drug therapy , Tumor Microenvironment
8.
J Colloid Interface Sci ; 662: 962-975, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38382379

ABSTRACT

This study involved the preparation of Metal Organic Frameworks (MOF)-derived Co8FeS8@Co1-xS nanoenzymes with strong interfacial interactions. The nanoenzymes presented the peroxidase (POD)-like activity and the oxidation activity of reduced glutathione (GSH). Accordingly, the dual activities of Co8FeS8@Co1-xS provided a self-cascading platform for producing significant amounts of hydroxyl radical (•OH) and depleting reduced glutathione, thereby inducing tumor cell apoptosis and ferroptosis. More importantly, the Co8FeS8@Co1-xS inhibited the anti-apoptosis protein B-cell lymphoma-2 (Bcl-2) and activated caspase family proteins, which caused tumor cell apoptosis. Simultaneously, Co8FeS8@Co1-xS affected the iron metabolism-related genes such as Heme oxygenase-1 (Hmox-1), amplifying the Fenton response and promoting apoptosis and ferroptosis. Therefore, the nanoenzyme synergistically killed anti-apoptotic tumor cells carrying Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Furthermore, Co8FeS8@Co1-xS demonstrated good biocompatibility, which paved the way for constructing a synergistic catalytic nanoplatform for an efficient tumor treatment.


Subject(s)
Ferroptosis , Neoplasms , Humans , Apoptosis , Neoplasms/drug therapy , Antioxidants , Glutathione/metabolism , Cell Line, Tumor , Hydrogen Peroxide
9.
eNeuro ; 11(2)2024 Feb.
Article in English | MEDLINE | ID: mdl-38351058

ABSTRACT

Spinal cord injury (SCI) has become one of the common and serious diseases affecting patients' motor functions. The small extracellular vesicles secreted by bone marrow mesenchymal stem cells (BMSCs) have shown a promising prospect for the treatment of neurological diseases. BMSCs were collected from rat bones. Osteogenic and adipogenic differentiation of BMSCs was further determined. Small extracellular vesicles were obtained by high-speed centrifugation. Dual-luciferase reporter assay was performed to demonstrate the targeting of miR-211-5p to the cyclooxygenase 2 (COX2) mRNA. qRT-PCR and Western blot assay were used for the detection of the mRNA and protein expression. ELISA was performed to estimate the levels of proinflammatory factors in spinal cord tissues. Our results showed that miR-211-5p targeted COX2 mRNA and regulated the protein expression of COX2 in BMSCs. Extracellular vesicles released from miR-211-5p-overexpressed BMSCs ameliorated SCI-induced motor dysfunction and motor evoked potential impairments. Extracellular vesicles released from miR-211-5p-overexpressed BMSCs ameliorated SCI-induced COX2 expression and related inflammatory responses. In conclusion, small extracellular vesicles released from miR-211-5p-overexpressed BMSCs ameliorate spinal cord injuries in rats.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , MicroRNAs , Spinal Cord Injuries , Rats , Humans , Animals , MicroRNAs/genetics , Cyclooxygenase 2/metabolism , Spinal Cord Injuries/therapy , Spinal Cord Injuries/metabolism , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , RNA, Messenger/metabolism
10.
Adv Healthc Mater ; 13(11): e2302556, 2024 04.
Article in English | MEDLINE | ID: mdl-38238011

ABSTRACT

Drug-induced liver injury (DILI) is a severe condition characterized by impaired liver function and the excessive activation of ferroptosis. Unfortunately, there are limited options currently available for preventing or treating DILI. In this study, MnO2 nanoflowers (MnO2Nfs) with remarkable capabilities of mimicking essential antioxidant enzymes, including catalase, superoxide dismutase (SOD), and glutathione peroxidase are successfully synthesized, and SOD is the dominant enzyme among them by density functional theory. Notably, MnO2Nfs demonstrate high efficiency in effectively eliminating diverse reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), superoxide anion (O2 •-), and hydroxyl radical (•OH). Through in vitro experiments, it is demonstrated that MnO2Nfs significantly enhance the recovery of intracellular glutathione content, acting as a potent inhibitor of ferroptosis even in the presence of ferroptosis activators. Moreover, MnO2Nfs exhibit excellent liver accumulation properties, providing robust protection against oxidative damage. Specifically, they attenuate acetaminophen-induced ferroptosis by inhibiting ferritinophagy and activating the P62-NRF2-GPX4 antioxidation signaling pathways. These findings highlight the remarkable ROS scavenging ability of MnO2Nfs and hold great promise as an innovative and potential clinical therapy for DILI and other ROS-related liver diseases.


Subject(s)
Chemical and Drug Induced Liver Injury , Ferroptosis , Manganese Compounds , Oxides , Reactive Oxygen Species , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Ferroptosis/drug effects , Oxides/chemistry , Animals , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Mice , Reactive Oxygen Species/metabolism , Oxidation-Reduction , Humans , Male , Acetaminophen , Liver/drug effects , Liver/metabolism , Liver/injuries , Liver/pathology , Antioxidants/pharmacology , Antioxidants/chemistry , Superoxide Dismutase/metabolism , Catalase/metabolism , Hydrogen Peroxide/metabolism , Mice, Inbred C57BL
11.
Environ Pollut ; 344: 123363, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38242309

ABSTRACT

Experiments were conducted to investigate the alleviating effects of ZnO quantum dots (ZnO QDs) on salt stress in Salvia miltiorrhiza by comparing them with conventional ZnO nanoparticles (ZnO NPs). The results demonstrated that compared with salt stress alone, foliar application of ZnO QDs significantly improved the biomass as well as the total chlorophyll and carotenoids contents under salt stress. ZnO QDs reduced H2O2 and MDA levels, decreased non-enzymatic antioxidant (ASA and GSH) content, and improved antioxidant enzyme (POD, SOD, CAT, PAL, and PPO) activity under salt stress. Metal elemental analysis further demonstrated that the ZnO QDs markedly increased Zn and K contents while decreasing Na content, resulting in a lower Na/K ratio compared to salt stress alone. Finally, RNA sequencing results indicated that ZnO QDs primarily regulated genes associated with stress-responsive pathways, including plant hormone signal transduction, the MAPK signaling pathway, and metabolic-related pathways, thereby alleviating the adverse effects of salt stress. In comparison, ZnO NPs did not exhibit similar effects in terms of improving plant growth, enhancing the antioxidant system, or regulating stress-responsive genes under salt stress. These findings highlight the distinct advantages of ZnO QDs and suggest their potential as a valuable tool for mitigating salt stress in plants.


Subject(s)
Salvia miltiorrhiza , Zinc Oxide , Reactive Oxygen Species , Zinc Oxide/toxicity , Antioxidants , Hydrogen Peroxide
12.
Eur Radiol ; 34(4): 2297-2309, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37707550

ABSTRACT

OBJECTIVES: To evaluate the ability of intraoperative CEUS to predict neurological recovery in patients with degenerative cervical myelopathy (DCM). METHODS: Twenty-six patients with DCM who underwent laminoplasty and intraoperative ultrasound (IOUS) were included in this prospective study. The modified Japanese Orthopaedic Association (mJOA) scores and MRI were assessed before surgery and 12 months postoperatively. The anteroposterior diameter (APD), maximum spinal cord compression (MSCC), and area of signal changes in the cord at the compressed and normal levels were measured and compared using MRI and IOUS. Conventional blood flow and CEUS indices (time to peak, ascending slope, peak intensity (PI), and area under the curve (AUC)) at different levels during IOUS were calculated and analysed. Correlations between all indicators and the neurological recovery rate were evaluated. RESULTS: All patients underwent IOUS and intraoperative CEUS, and the total recovery rate was 50.7 ± 33.3%. APD and MSCC improved significantly (p < 0.01). The recovery rate of the hyperechoic lesion group was significantly worse than that of the isoechoic group (p = 0.016). 22 patients were analysed by contrast analysis software. PI was higher in the compressed zone than in the normal zone (24.58 ± 3.19 versus 22.43 ± 2.39, p = 0.019). ΔPI compress-normal and ΔAUC compress-normal of the hyperechoic lesion group were significantly higher than those of the isoechoic group (median 2.19 versus 0.55, p = 0.017; 135.7 versus 21.54, p = 0.014, respectively), and both indices were moderately negatively correlated with the recovery rate (r = - 0.463, p = 0.030; r = - 0.466, p = 0.029). CONCLUSIONS: Signal changes and microvascular perfusion evaluated using CEUS during surgery are valuable predictors of cervical myelopathy prognosis. CLINICAL RELEVANCE STATEMENT: In the spinal cord compression area of degenerative cervical myelopathy, especially in the hyperechoic lesions, intraoperative CEUS showed more significant contrast agent perfusion than in the normal area, and the degree was negatively correlated with the neurological prognosis. KEY POINTS: • Recovery rates in patients with hyperechoic findings were lower than those of patients without lesions detected during intraoperative ultrasound. • The peak intensity of CEUS was higher in compressed zones than in the normal parts of the spinal cord. • Quantitative CEUS comparisons of the peak intensity and area under the curve at the compressed and normal levels of the spinal cord revealed differences that were inversely correlated to the recovery rate.


Subject(s)
Cervical Cord , Spinal Cord Compression , Spinal Cord Diseases , Humans , Spinal Cord Compression/pathology , Prospective Studies , Cervical Cord/diagnostic imaging , Cervical Cord/surgery , Cervical Cord/pathology , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Cervical Vertebrae/pathology , Spinal Cord/pathology , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/surgery , Spinal Cord Diseases/pathology , Magnetic Resonance Imaging , Treatment Outcome
13.
Small ; 20(1): e2304438, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37661593

ABSTRACT

The cell elimination strategy based on reactive oxygen species (ROS) is a promising method for tumor therapy. However, its efficacy is significantly limited by ROS deficiency caused by H2 O2 substrate deficiency and up-regulation of cellular antioxidant defense induced by high glutathione (GSH) content in tumor cells. To overcome these obstacles, a multifunctional self-cascaded nanocomposite: glucose oxidase (GOX) loaded NaYF4 :Yb/Er@Mn3 O4 (UC@Mn3 O4 , labeled as UCMn) is constructed. Only in tumor microenvironment, it can be specifically activated through a series of cascades to boost ROS production via a strategy of open source (H2 O2 self-supplying ability). The increased ROS can enhance lipid peroxidation and induce tumor cell apoptosis by activating the protein caspase. More importantly, the nanozyme can consume GSH to inhibit glutathione peroxidase 4 (GPX4) activity, which limits tumor cell resistance to oxidative damage and triggers the tumor cell ferroptosis. Therefore, this strategy is expected to overcome the resistance of tumor to oxidative damage and achieve efficient oxidative damage of tumor. Further, degradation of the Mn3 O4 layer induced by GSH and acidic environment can promote the fluorescence recovery of UC fluorescent nuclear for tumor imaging to complete efficient integration of diagnosis and treatment for tumor.


Subject(s)
Ferroptosis , Nanocomposites , Neoplasms , Humans , Glucose Oxidase , Reactive Oxygen Species , Apoptosis , Optical Imaging , Antioxidants , Glutathione , Neoplasms/therapy , Cell Line, Tumor , Tumor Microenvironment , Hydrogen Peroxide
14.
Fitoterapia ; 173: 105786, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38135093

ABSTRACT

Four kinds of tea polysaccharides (MBTPS, MGTPS, ZBTPS, ZGTPS) were extracted from Maofeng black tea, Maofeng green tea,Ziyan black tea and Ziyan green tea, and then four tea polysaccharides (RMBTPS, RMGTPS, RZBTPS, RZGTPS) after metal removal were prepared. The physicochemical properties, antioxidant activity and inhibitory activity on cancer cell proliferation of the above polysaccharides were studied. The composition analysis shows that these tea polysaccharides were glycoproteins complexes, composed of a variety of monosaccharides, and the removal of metal ions did not lead to fundamental changes in the composition of polysaccharides. In vitro activity, after removing metal ions, the ABTS free radicals scavenging ability and reducing power of tea polysaccharides were decreased, and the inhibitory effect on proliferation of H22 cells weakened. There was a great correlation between metal elements Al and Ni and biological activity. The results showed that the metal ions in tea polysaccharides, especially Al and Ni, had positive effects on biological activity.


Subject(s)
Antioxidants , Neoplasms , Antioxidants/pharmacology , Antioxidants/chemistry , Molecular Structure , Polysaccharides/pharmacology , Polysaccharides/chemistry , Tea/chemistry , Metals/chemistry , Ions
15.
Small ; 20(17): e2309593, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38126566

ABSTRACT

The clinical application of oncology therapy is hampered by high glutathione concentrations, hypoxia, and inefficient activation of cell death mechanisms in cancer cells. In this study, Fe and Mo bimetallic sulfide nanomaterial (FeS2@MoS2) based on metal-organic framework structure is rationally prepared with peroxidase (POD)-, catalase (CAT)-, superoxide dismutase (SOD)-like activities and glutathione depletion ability, which can confer versatility for treating tumors and mending wounds. In the lesion area, FeS2@MoS2 with SOD-like activity can facilitate the transformation of superoxide anions (O2 -) to hydrogen peroxide (H2O2), and then the resulting H2O2 serves as a substrate for the Fenton reaction with FMS to produce highly toxic hydroxyl radicals (∙OH). Simultaneously, FeS2@MoS2 has an ability to deplete glutathione (GSH) and catalyze the decomposition of nicotinamide adenine dinucleotide phosphate (NADPH) to curb the regeneration of GSH from the source. Thus it can realize effective tumor elimination through synergistic apoptosis-ferroptosis strategy. Based on the alteration of the H2O2 system, free radical production, glutathione depletion and the alleviation of hypoxia in the tumor microenvironment, FeS2@MoS2 NPS can not only significantly inhibit tumors in vivo and in vitro, but also inhibit multidrug-resistant bacteria and hasten wound healing. It may open the door to the development of cascade nanoplatforms for effective tumor treatment and overcoming wound infection.


Subject(s)
Antineoplastic Agents , Metal-Organic Frameworks , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/chemistry , Cell Line, Tumor , Mice , Glutathione/metabolism , Iron/chemistry , Iron/metabolism , Apoptosis/drug effects , Molybdenum/chemistry , Molybdenum/pharmacology , Nanostructures/chemistry , Ferroptosis/drug effects
16.
J Pain Res ; 16: 2861-2869, 2023.
Article in English | MEDLINE | ID: mdl-37609360

ABSTRACT

Objective: This study aimed to explore the related risk factors in patients who underwent hemilaminectomy for lumbar spinal schwannoma resection and who experienced deterioration of postoperative lower back pain in comparison to preoperative pain levels. Methods: This retrospective study recruited 61 patients from the First Affiliated Hospital of An Hui Medical University between January 2018 and June 2019. All data were collected from clinical records and analyzed at 1-month and at 1-year follow-up. The visual analog scale (VAS) was used to evaluate pain, and neurologic function was assessed using the Modified McCormick Scale. Intraoperative neurophysiological monitoring was used to assess neuronal integrity and mitigate injury. Statistical analysis of the data was performed using the SPSS version 19 software. Results: Preoperative pain improved dramatically in the 1-year follow-up (VAS: preoperative, 3.84±2.19; 1-year follow-up, 2.13±2.26; P<0.001). The pain-improved group and worsened group showed a significant difference at 1-month (VAS: 1.76±1.56; 5.54±1.26; P<0.05) and at 1-year (VAS: 0.83±1.09; 4.80±1.58; P<0.05) follow-up. The pain-improved and worsened groups had a significant difference in tumor size and hemilaminectomy removal segments at 1-month and 1-year follow-up, but A-train occurrence on electromyography could only be seen as a statistical difference in the 1-month follow-up. Logistic regression analysis revealed that tumor size was an independent risk factor for postoperative lower back pain deterioration. Conclusion: The hemilaminectomy approach is a safe and effective method that can dramatically relieve pain in spinal lumbar schwannoma resection. Tumor size is an independent risk factor for postoperative lower back pain. A-train on spontaneous electromyography has been shown to be a reliable predictive factor for the evaluation of postoperative lower back pain. However, further detailed analysis of A-train characteristics can provide a more accurate warning during surgery.

17.
ACS Appl Mater Interfaces ; 15(28): 33273-33287, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37410395

ABSTRACT

When reactive oxygen species (ROS) accumulate in the body, they can lead to inflammatory bowel disease (IBD) through their oxidative damages to DNA, proteins, and lipids. In this study, a thermosensitive hydrogel-based nanozyme was developed to treat IBD. We first synthesized a manganese oxide (Mn3O4) nanozyme with multienzyme activity followed by physically loading with a thermosensitive hydrogel poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide)-based triblock copolymer (PDLLA-PEG-PDLLA). Then, a mouse model based on the inducement of dextran sulfate sodium (DSS) was built to assess the ROS targeting, scavenging, as well as anti-inflammatory ability of Mn3O4 nanozymes-loaded PDLLA-PEG-PDLLA (MLPPP). Because of the sharp gelation behavior of PDLLA-PEG-PDLLA in body temperature, the MLPPP nanozyme can easily target the inflamed colon after colorectal administration. Following the formation of a physical protection barrier and sustained release of manganese oxide nanozymes that had diverse enzymatic activities and can effectively scavenge ROS, the administration of the MLPPP nanozyme had a high efficacy for treating colitis mice; importantly, after the treatment with this novel nanoformulation, the levels of the pathological indicators in colons as well as in sera of colitis mice were even comparable to healthy mice. Therefore, the MLPPP nanozyme has a potential application for nanotherapy of IBD and would have great clinical translation prospects.


Subject(s)
Colitis , Inflammatory Bowel Diseases , Mice , Animals , Polyesters , Reactive Oxygen Species , Inflammatory Bowel Diseases/drug therapy , Hydrogels , Polyethylene Glycols
18.
Molecules ; 28(13)2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37446776

ABSTRACT

Streptococcus agalactiae is a significant pathogen that can affect both human beings and animals. The extensive current use of antibiotics has resulted in antibiotic resistance. In our previous research, we found that zinc oxide quantum dots (ZnO QDs) had inhibitory effects on antibiotic-resistant microorganisms. In this study, a strain of Streptococcus agalactiaeWJYT1 with a broad antibiotic-resistant spectrum was isolated and identified from Lama glama at Sichuan Agricultural University Teaching Animal Hospital. The genome for the resistance and virulence genes was analyzed. Additionally, the antibacterial effects and anti-virulence mechanism of ZnO QDs for S. agalactiaeWJYT1 were investigated. The results showed that the genome of S. agalactiaeWJYT1 is 1,943,955 bp, containing 22 resistance genes and 95 virulence genes. ZnO QDs have a good antibacterial effect against S. agalactiaeWJYT1 by reducing bacterial growth and decreasing the expression of virulence genes, including bibA, hylB, sip, and cip, which provides a novel potential treatment for S. agalactiae.


Subject(s)
Camelids, New World , Quantum Dots , Streptococcal Infections , Zinc Oxide , Humans , Animals , Streptococcus agalactiae , Zinc Oxide/pharmacology , Anti-Bacterial Agents/pharmacology , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology
19.
Anal Chim Acta ; 1251: 340983, 2023 Apr 22.
Article in English | MEDLINE | ID: mdl-36925281

ABSTRACT

Dual-signal ratiometric molecularly imprinted polymer (MIP) electrochemical sensors with bimetallic active sites and high-efficiency catalytic activity were fabricated for the sensing of catechol (CC) with high selectivity and sensitivity. The amino-functionalization bimetallic organic framework materials (Fe@Ti-MOF-NH2), coupled with two-dimensional layered titanium carbide (MXene) co-modified glassy carbon electrode provides an expanded surface while amplifying the output signal through the electropolymerization immobilization of polythionine (pTHi) and MIP. The oxidation of CC and pTHi were presented as the response signal and the internal reference signal. The oxidation peak current at +0.42 V rose with increased concentration of CC, while the peak currents of pTHi at -0.20 V remained constant. Compared to the common single-signal sensing system, this one (MIP/pTHi/MXene/Fe@Ti-MOF-NH2/GCE), a novel ratiometric MIP electrochemical sensor exhibited two segments wide dynamic range of 1.0-300 µM (R2 = 0.9924) and 300-4000 µM (R2 = 0.9912), as well as an ultralow detection limit of 0.54 µM (S/N = 3). Due to the specific recognition function of MIPs and the advantages of built-in correction of pTHi, the prepared surface imprinting sensor presented an excellent performance in selectivity and reproducibility. Besides, this sensor possessed superior anti-interference ability with ions and biomolecules, excellent reproducibility, repeatability, and acceptable stability. Furthermore, the proposed sensing system exhibits high specific recognition in the determination of environmental matrices and biological fluids in real samples with satisfactory results. Therefore, this signal-enhanced ratiometric MIP electrochemical sensing strategy can accurately and selectively analyze and detect other substances.


Subject(s)
Molecular Imprinting , Molecular Imprinting/methods , Reproducibility of Results , Carbon , Catechols , Electrochemical Techniques/methods , Limit of Detection , Electrodes
20.
Article in English | MEDLINE | ID: mdl-36750421

ABSTRACT

An optical monitoring device combining a smartphone with a polychromatic ratiometric fluorescence-colorimetric paper sensor was developed to detect Hg2+ and S2- in water and seafood. This monitoring included the detection of food deterioration and was made possible by processing the sensing data with a machine learning algorithm. The polychromatic fluorescence sensor was composed of blue fluorescent carbon quantum dots (CDs) (BU-CDs) and green and red fluorescent CdZnTe quantum dots (QDs) (named GN-QDs and RD-QDs, respectively). The experimental results and density functional theory (DFT) prove that the incorporation of Zn can improve the stability and quantum yield of CdZnTe QDs. According to the dynamic and static quenching mechanisms, GN-QDs and RD-QDs were quenched by Hg2+ and sulfide, respectively, but BU-CDs were not sensitive to them. The system colors change from green to red to blue as the concentration of the two detectors rises, and the limits of detection (LOD) were 0.002 and 1.488 µM, respectively. Meanwhile, the probe was combined with the hydrogel to construct a visual sensing intelligent test strip, which realized the monitoring of food freshness. In addition, a smartphone device assisted by multiple machine learning methods was used to text Hg2+ and sulfide in real samples. It can be concluded that the fabulous stability, sensitivity, and practicality exhibited by this sensing mechanism give it unlimited potential for assessing the contents of toxic and hazardous substances Hg2+ and sulfide.

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