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1.
Artigo em Inglês | MEDLINE | ID: mdl-38916723

RESUMO

BACKGROUND: The purpose of this study was to identify the possible association between mental status and the risk of self-reported asthenopia among college students in China. METHODS: Ten thousand students were randomly assessed in the study using a self-reported asthenopia questionnaire. Their demographic characteristics and mental status were recorded. Univariate analysis was performed to preliminarily select potential risk and protective factors. Then, multivariate logistic regression was used to estimate odds ratios for the selected risk factors of interest. RESULTS: Among the 8370 students who completed the survey, the prevalence of asthenopia was 61.0%. Multivariate analysis revealed a significant relationship between asthenopia and depressive symptoms (OR 1.511 95% CI: 1.350-1.691), obsessive-compulsive symptoms (OR 1.477, 95% CI: 1.338-1.632), gender and study load. The place college students spent their off-hours (OR 0.841, 95% CI: 0.784-0.902) was found to be the strongest factor for decreasing the occurrence of asthenopia complaints. CONCLUSION: Asthenopia appears common in Chinese college students. In addition to depressive symptoms, we should pay attention to obsessive-compulsive symptoms when considering means of preventing asthenopia. Harmonious social relationships, outdoor off-hour activities and exercising more than three times per week are crucial to relieving visual fatigue. Further study is still needed in this area.

2.
Transl Androl Urol ; 13(4): 526-536, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38721282

RESUMO

Background: Nephrolithiasis seriously affects people's health with increasing prevalence and high recurrence rates. However, there is still a lack of effective interventions for the clinical prevention of kidney stones. Hyperoxaluria-induced renal tubular epithelial cell (TEC) injury is a known key factor in kidney stone formation. Thus, developing new drugs to inhibit the hyperoxaluria-induced TEC injury may be the best way. Methods: We synthesized the Se@SiO2 nanocomposites as described in Zhu's study. The size and morphology of the Se@SiO2 nanocomposites were captured by transmission electron microscopy. Cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. The mice were randomly divided into the following four groups: (I) the control group (n=6); (II) the Se@SiO2 group (n=6); (III) the glyoxylic acid monohydrate (GAM) group; and (IV) the GAM + Se@SiO2 group (n=6). The concentration of Se in the mice was quantified using inductively coupled plasma atomic emission spectroscopy. Results: The CCK-8 assays showed that Se@SiO2 nanocomposites had almost no obvious cytotoxicity on the Transformed C3H Mouse Kidney-1 (TCMK-1) cell. The mice kidney Se concentration levels in the Se@SiO2 groups (Se@SiO2 6.905±0.074 mg/kg; GAM + Se@SiO2 7.673±2.85 mg/kg) (n=6) were significantly higher than those in the control group (Control 0.727±0.072 mg/kg; GAM 0.747±0.074 mg/kg) (n=6). The Se@SiO2 nanocomposites reduced kidney injury, calcium oxalate crystal deposition, and the osteoblastic-associated proteins in the hyperoxaluria mice models. Conclusions: Se@SiO2 nanocomposites appear to protect renal TECs from hyperoxaluria by reducing reactive oxygen species production, suggesting the potential role of preventing kidney stone formation and recurrence.

3.
Int Dent J ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631944

RESUMO

OBJECTIVES: Investigate the geographical distribution of private dental practices in major Chinese cities and analyze the variables influencing this distribution. METHODS: This study used Python to extract various types of Point of Interest (POI) data spanning from 2016 to 2022 from the AutoNavi map. A 1km*1km grid was constructed to establish the study sample. Additional spatial pattern data, including nighttime lighting, population, and air quality data, were integrated into this grid. Global Moran's I index was used to analyze the spatial autocorrelation. The spatial lag model was used to explore the influencing factors of private dental practice distribution. RESULTS: This study reveals a specific clustering pattern for private dental practices in major Chinese cities. The primary influencing factors include nighttime lights, population density, and housing prices, suggesting that dental practices are typically concentrated in highly developed regions with dense populations and high housing costs. Additionally, we discovered that patterns vary across different metropolises, with the most pronounced clustering patterns and substantial inequalities found in the most developed areas. CONCLUSIONS: This study establishes that factors such as regional development and population density positively correlate with private dental practice. Additionally, it reveals a strong mutual correlation in the clustering of dental practices, which does not show a substantial correlation with public resources. Finally, it suggests that the spatial heterogeneity pattern implies a rising necessity to tackle inequality issues within urban areas as economic development progresses.

4.
Front Cell Infect Microbiol ; 13: 1256866, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38029253

RESUMO

Introduction: Healthy lung microbiota plays an important role in preventing Mycobacterium tuberculosis (Mtb) infections by activating immune cells and stimulating production of T-helper cell type 1 cytokines. The dynamic stability of lung microbiota relies mostly on lung homeostasis. In our previous studies, we found that Mtb virulence factor, Rv1987 protein, can mediate host immune response and enhance mycobacterial survival in host lung. However, the alteration of lung microbiota and the contribution of lung microbiota dysbiosis to mycobacterial evasion in this process are not clear so far. Methods: M. smegmatis which does not contain the ortholog of Rv1987 protein was selected as a model strain to study the effects of Rv1987 on host lung microbiota. The lung microbiota, immune state and metabolites of mice infected by M. smegmatis overexpressing Rv1987 protein (MS1987) were detected and analyzed. Results: The results showed that Rv1987 inhibited inflammatory response in mouse lung and anaerobic bacteria and Proteobacteria, Bacteroidota, Actinobacteriota and Acidobacteriota bacteria were enriched in the lung tissues correspondingly. The immune alterations and microbiota dysbiosis affected host metabolic profiles, and some of significantly altered bacteria in MS1987-infected mouse lung, such as Delftia acidovorans, Ralstonia pickettii and Escherichia coli, led to anti-inflammatory responses in mouse lung. The secretory metabolites of these altered bacteria also influenced mycobacterial growth and biofilm formation directly. Conclusion: All these results suggested that Rv1987 can attenuate inflammatory response and alter microbiota in the lung, which in turn facilitates mycobacterial survival in the host.


Assuntos
Microbiota , Infecções por Mycobacterium , Mycobacterium tuberculosis , Animais , Camundongos , Disbiose/microbiologia , Citocinas/metabolismo , Pulmão/microbiologia
5.
J Mater Chem B ; 11(38): 9300-9310, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37727911

RESUMO

The problems of bacterial resistance and high oxidation level severely limit wound healing. Therefore, we constructed a multifunctional platform of chitosan quaternary ammonium salts (QCS)/polyvinyl alcohol (PVA)/polyethylene glycol (PEG) hydrogels (QPP) loaded with ZnO@CeO2 (ZC-QPP). Firstly, the hydrogel was co-cross-linked by hydrogen and borate ester bonds, which allows easy adherence to a tissue surface for offering a protective barrier and moist environment for wounds. The chitosan quaternary ammonium salts due to their amino groups have inherent antibacterial properties to induce bacterial death. In response to the acidic conditions of the bacterial infection microenvironment, the borate ester bonds in the QPP hydrogel break and the ZC NCs dispersed in the hydrogel are released. The gradual dissociation of Zn2+ under acidic conditions can directly damage bacterial membranes. The wound site of bacterial infection always causes overexpression of reactive oxygen species (ROS) levels, often leading to inflammation and preventing rapid wound repair. CeO2 can eliminate excess ROS to reduce the inflammatory response. From in vitro and in vivo results, the high biosafety of the ZC-QPP hydrogel has demonstrated excellent antibacterial and antioxidant performance to enhance wound healing. Therefore, the ZC-QPP hydrogel opens a method to develop multifunctional synergistic therapeutic platforms combining enzyme-like nanomaterials with hydrogels for synergistic antibacterial and antioxidant treatment to promote wound healing.

6.
BMC Nurs ; 22(1): 311, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700328

RESUMO

BACKGROUND: A shortage of qualified nurses and their low level of educational qualifications hinders the development of global health services. Studies have proven the role of nursing education in addressing these problems. However, no related studies have focused on senior high school students in China. This study aimed to explore senior high school students' intentions to learn nursing and identify the factors influencing their decision-making processes. METHODS: An anonymous questionnaire was distributed to 8050 senior high school students, which included questions regarding their demographic characteristics, obtaining nursing specialty information, cognition of the nursing occupation and the impact of the COVID-19 on the nursing profession. Descriptive calculation, the chi-square test and logistic regression were used for the analysis. RESULTS: Only 0.73% of the participants had a clear intention to study nursing. Academic performance and family support were significant predictors of students' intentions to pursue nursing education. Students' interest in nursing specialties was associated with their choice. There was a positive correlation between cognition of nursing occupation and students' choice of nursing. Students' experience of the COVID-19 pandemic also had a positive impact on their nursing career choice. CONCLUSION: This survey to some extent reflects the problem of nurses shortage in China. In addition, these findings may also provide a new perspective for predictors of nursing shortage and potential interventions.

7.
BMC Musculoskelet Disord ; 24(1): 641, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559076

RESUMO

BACKGROUND: After the COVID-19 outbreak, many Chinese high school students have increased their dependence on electronic devices for studying and life, which may affect the incidence of neck and shoulder pain (NSP) in Chinese adolescents. METHODS: To evaluate the prevalence of NSP in high school students and its associated risk factors during COVID-19, a survey was conducted among 5,046 high school students in Shanghai, Qinghai, Henan and Macao during the second semester and summer vacation of the 2019-2020 academic year. The questionnaire included questions regarding demographic characteristics, the prevalence of NSP and lifestyle factors such as sedentary behavior, poor posture and electronic device usage. Univariable and multivariable logistic regression was used to analyze the possible influencing factors for neck and shoulder pain. RESULTS: A total of 4793 valid questionnaires (95.0%) were collected. The results indicated that the prevalence of NSP was 23.7% among high school students. Binary logistic regression analysis revealed that female gender (P < 0.05, OR = 1.82), grade (P < 0.05, range OR 1.40-1.51) and subject selection (P < 0.05, range OR 0.49-0.68) were risk factors for NSP in high school students. Sedentary behavior (P < 0.05, range OR 1.74-2.36), poor posture (P < 0.05, range OR 1.19-2.56), backpack weight (P < 0.05, range OR 1.17-1.88), exercise style and frequency (P < 0.05, range OR 1.18-1.31; P < 0.05, range OR 0.76-0.79, respectively), and the time spent using electronic devices (P < 0.05, range OR 1.23-1.38)had a significant correlation with NSP in high school students. CONCLUSIONS: NSP is currently very common among high school students during the outbreak of COVID-19. Sedentary behavior, poor posture and other factors have a great impact on the occurrence of NSP in high school students. Education regarding healthy lifestyle choices should be advocated for to decrease NSP among high school students, such as more physical activity, changing poor postures and reducing the amount of time spent using electronic devices.


Assuntos
COVID-19 , Dor de Ombro , Adolescente , Humanos , Feminino , Dor de Ombro/diagnóstico , Dor de Ombro/epidemiologia , Dor de Ombro/etiologia , Estudos Transversais , Cervicalgia/etiologia , Prevalência , China/epidemiologia , COVID-19/epidemiologia , Fatores de Risco , Estudantes , Inquéritos e Questionários
8.
Oxid Med Cell Longev ; 2023: 7773609, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778204

RESUMO

An imbalance in oxidative and inflammatory regulation is the main contributor to intervertebral disc degeneration (IDD). Hydrogen (H2) therapy is a promising antioxidation and anti-inflammatory approach. However, the key to the treatment is how to maintain the long-term effective H2 concentration in the intervertebral disc (IVD). Therefore, we developed a pH-responsive delivery of H2 through ammonia borane-loaded hollow polydopamine (AB@HPDA) for IDD therapy, which has sufficient capacity to control long-term H2 release in an acid-dependent manner in degenerative IVD. The characterization, toxicity, and pH-responsive H2 release of AB@HPDA was detected in vitro. The metabolization of AB@HPDA in the degenerated IVD was tested by in vivo imaging. The therapeutic effect of AB@HPDA on IDD was tested in vivo by X-ray, MRI, water content of the disc, and histological changes. Nuclear extracellular matrix (ECM) components, oxidative stress, and inflammation were also tested to explore potential therapeutic mechanisms. AB@HPDA has good biocompatibility at concentrations less than 500 µg/mL. The H2 release of AB@HPDA was pH responsive. Therefore, AB@HPDAs can provide efficient hydrogen therapy with controlled H2 release in response to the acidic degenerated IVD microenvironment. The metabolization of AB@HPDA in IVD was slow and lasted up to 11 days. HPDA and AB@HPDA significantly inhibited IDD, as tested by X-ray, MRI, disc water content, and histology (P < 0.05). pH-responsive H2 delivery through AB@HPDAs has the potential to efficiently treat IDD by inhibiting ECM degradation and rebalancing oxidative stress and inflammation in degenerative IVDs.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Degeneração do Disco Intervertebral/patologia , Amônia/metabolismo , Amônia/uso terapêutico , Disco Intervertebral/metabolismo , Inflamação/patologia , Concentração de Íons de Hidrogênio
9.
Orthop Surg ; 15(8): 2152-2156, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36349872

RESUMO

OBJECTIVE: Implant failure is a disastrous complication of the operative treatment of midshaft clavicle fractures, and improving the osteosynthesis plate is a strategy for preventing this. We aimed to investigate whether canceling the notch and adding screw-hole inserts enhanced the mechanical properties of the plate. METHODS: A clavicle model was generated based on the CT images of six adult volunteers (age range, 20-40 years; three males and three females; height range 160-175) using dedicated software, and a midshaft fracture model was created. The domestically made seven-hole locking plate commonly used for midshaft clavicle fractures was simulated (Model I); modifications were made to the plate (Model II). Using 3D finite element analysis, we simulated the fracture construct under three different load conditions-downward cantilever bending, axial compression, and axial torsion-and compared the stress distribution. RESULTS: We found that under axial compression, Model II experienced its maximum stress on the plate at 551.9MPa, which was less than that in Model I (790.4 MPa). Moreover, a greater stress concentration at the fracture site was observed under axial torsion, despite the maximum stress of both the models being similar. CONCLUSION: Canceling the notch and filling the screw holes near the fracture can ameliorate stress concentration on the internal fixation construct and enhance its reliability under axial compression. This improvement has substantial effects on the mechanical properties of implants and potentially prevents implant failure. Modern osteosynthesis anatomical implants need to be improved.


Assuntos
Clavícula , Fraturas Ósseas , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Clavícula/cirurgia , Análise de Elementos Finitos , Reprodutibilidade dos Testes , Fenômenos Biomecânicos , Fixação Interna de Fraturas/métodos , Placas Ósseas , Fraturas Ósseas/cirurgia
10.
Metabolites ; 12(10)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36295794

RESUMO

The disturbance in gut microbiota composition and metabolism has been implicated in the process of pathogenic bacteria infection. However, the characteristics of the microbiota and the metabolic interaction of commensals−host during pathogen invasion remain more than vague. In this study, the potential associations of gut microbes with disturbed lipid metabolism in mice upon carbapenem-resistant Escherichia coli (CRE) infection were explored by the biochemical and multi-omics approaches including metagenomics, metabolomics and lipidomics, and then the key metabolites−reaction−enzyme−gene interaction network was constructed. Results showed that intestinal Erysipelotrichaceae family was strongly associated with the hepatic total cholesterol and HDL-cholesterol, as well as a few sera and fecal metabolites involved in lipid metabolism such as 24, 25-dihydrolanosterol. A high-coverage lipidomic analysis further demonstrated that a total of 529 lipid molecules was significantly enriched and 520 were depleted in the liver of mice infected with CRE. Among them, 35 lipid species showed high correlations (|r| > 0.8 and p < 0.05) with the Erysipelotrichaceae family, including phosphatidylglycerol (42:2), phosphatidylglycerol (42:3), phosphatidylglycerol (38:5), phosphatidylcholine (42:4), ceramide (d17:1/16:0), ceramide (d18:1/16:0) and diacylglycerol (20:2), with correlation coefficients higher than 0.9. In conclusion, the systematic multi-omics study improved the understanding of the complicated connection between the microbiota and the host during pathogen invasion, which thereby is expected to lead to the future discovery and establishment of novel control strategies for CRE infection.

11.
Eur Spine J ; 31(11): 2960-2971, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36152221

RESUMO

PURPOSE: Discoblock is effective in relieving discogenic low back pain, but it can also cause intervertebral disk degeneration (IDD). The effect of species, concentration and volume of local anesthetics on IDD with discoblock have not been reported. The purpose was to study the effect of species, concentration and volume of local anesthetics on IDD in rats undergoing discoblock. METHODS: The effects of local anesthetics on nucleus pulposus cell (NPC) viability in vitro were studied. NPCs were exposed to lidocaine, bupivacaine and ropivacaine at different concentrations. NPC viability was measured. The least cytotoxic local anesthetic was used in vivo. The concentration and volume of local anesthetics on IDD in rat with discoblocks were tested in vivo. Detection indicators included X-ray, MRI, water content of the disk and histological changes. RESULTS: The toxicity of local anesthetics to NPCs was dose and time dependent, and the cytotoxicity of different local anesthetics was different. Among the three local anesthetics, ropivacaine was the least toxic to NPCs. The effect of ropivacaine concentration on IDD was not significant, as detected by X-ray, MRI, disk water content and histology (P < 0.05). The volume of ropivacaine has a significant effect on IDD, as supported by X-ray, MRI, disk water content and histology (P < 0.05). Acupuncture itself significantly increased IDD, as detected by MRI, disk water content and histology (P < 0.05). CONCLUSION: Ropivacaine should be selected for its low cytotoxicity. A lower volume and slow injection speed should be used to reduce IDD during discoblock.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Ratos , Animais , Anestésicos Locais/farmacologia , Degeneração do Disco Intervertebral/patologia , Ropivacaina/farmacologia , Disco Intervertebral/patologia , Água
12.
J Pharm Biomed Anal ; 215: 114770, 2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35489247

RESUMO

Increasing evidence highlighted the metabolic associations between host and gut microbiota during infection. However, how host-gut microbiota metabolic partnership response to carbapenem-resistant Escherichia coli (CRE) infection has yet to be elucidated. In this study, we subjected the mice to a single intraperitoneal injection of CRE and studied the alterations of the small molecule metabolites derived from host-microbial co-metabolism, as well as the gut microbiome in mice, at 24 h after infection by a two-level strategy. A panel of metabolites in feces and serum, were found to alter significantly in the CRE group, including 26 joint metabolites between them. Meanwhile, the relative abundance of 14 OTUs in Firmicutes (10 OTU), Bacteroidetes (2 OTU), Actinomycetes (1 OTU), and Proteobacteria (1 OTU) were observed to change after infection. Association analyses demonstrated that 9 OTUs including six in the Firmicutes phylum, two in the Bacteroidetes phylum, and one in the Actinomycetes phylum, were associated with the changes of 49 fecal metabolites and 42 serum metabolites. The study of gut microbiota-host metabolic interactions in the early stage of the infection is expected to provide novel diagnostic methods and therapeutic strategies for CRE infection, bring innovative solutions to resolve the current challenge.


Assuntos
Infecções por Escherichia coli , Microbioma Gastrointestinal , Animais , Carbapenêmicos/farmacologia , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Fezes/microbiologia , Metaboloma , Camundongos , RNA Ribossômico 16S
13.
Front Bioeng Biotechnol ; 10: 852482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35387298

RESUMO

Hypertrophic scarring, which is characterized by excessive extracellular matrix deposition and abnormal fibroblast homeostasis, is an undesirable outcome of dermal wound healing. Once formed, the scar will replace the normal function of local skin, and there are few noninvasive clinical treatments that can cure it. Se@SiO2 nanoparticles were synthesized to suppress oxidative stress, which induced the presence and activation of myofibroblasts during wound recovery. The characterization, antioxidant capacity and biological safety of Se@SiO2 NPs were evaluated. A full-thickness excisional wound model was established, and the wounds were divided into three groups. The re-epithelization and distribution of collagen fibers were assessed using hematoxylin and eosin staining and Masson's trichome staining after specific treatments. Our results revealed that the Se@SiO2 NPs accelerated dermal wound healing and suppressed the formation of hypertrophic scars, accompanied by oxidative stress inhibition. Moreover, we found that Se@SiO2 NPs worked by activating the PI3K/Akt pathway and upregulating the phosphorylation of Akt. The findings of our study provide a new method to promote dermal scar-free wound healing by suppressing excessive oxidative stress and through PI3K/Akt pathway activation.

14.
ACS Biomater Sci Eng ; 8(3): 1342-1353, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35230821

RESUMO

Radiotherapy has been widely used to manage primary and metastatic brain tumors. However, hippocampal damage and subsequent cognitive dysfunction are common complications of whole brain radiation (WBI). In this study, Se@SiO2 nanoparticles (NPs) with antioxidant properties were synthesized. Se@SiO2 NPs were characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM). The reactive oxygen species (ROS) scavenging ability of Se@SiO2 NPs was assessed using a dichloro-dihydro-fluorescein diacetate (DCFH-DA) probe. Apoptosis of HT-22 cells treated with H2O2 and Se@SiO2 NPs was assessed by annexin V-FITC/PI and JC-1 staining. Western blotting was used to evaluate inflammation-related signaling pathways. In vivo, the distribution and excretion of Se@SiO2 NPs were assessed using in vivo imaging system (IVIS). The biosafety and antioxidant effects of Se@SiO2 NPs were assessed. Neurogenesis in the hippocampus of mice was detected through neuron-specific nuclear protein (NeuN) and 5-bromo-2'-deoxyuridine (BrdU) immunofluorescence staining. The cognitive abilities of mice were also assessed using the Morris water maze test. Results showed that porous Se@SiO2 NPs were successfully synthesized with uniform spherical structures. In vitro, Se@SiO2 NPs inhibited ROS levels in mouse hippocampal neuronal cell line HT-22 treated with H2O2. Furthermore, Se@SiO2 NPs suppressed the apoptotic rate of HT-22 cells by regulating apoptosis-related proteins. Se@SiO2 NPs regulated the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby reducing the expression of inflammatory factors. In vivo, Se@SiO2 NPs showed high biocompatibility at a concentration of 1.25 µg/µL. Se@SiO2 NPs inhibited ROS and promoted neurogenesis in the hippocampus, as well as improved cognitive ability in radiation-induced mice. In conclusion, Se@SiO2 NPs protected the hippocampus from oxidative stress injury and neuroinflammation. Se@SiO2 NPs treatment may be a potential therapeutic strategy for radiation-induced cognitive dysfunction.


Assuntos
Disfunção Cognitiva , Nanopartículas , Animais , Peróxido de Hidrogênio , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Porosidade , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Dióxido de Silício/farmacologia
15.
Small ; 18(13): e2107160, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35146899

RESUMO

Emerging noninvasive treatments, such as sonodynamic therapy (SDT) and chemodynamic therapy (CDT), have developed as promising alternatives or supplements to traditional chemotherapy. However, their therapeutic effects are limited by the hypoxic environment of tumors. Here, a biodegradable nanocomposite-mesoporous zeolitic-imidazolate-framework@MnO2 /doxorubicin hydrochloride (mZMD) is developed, which achieves enhanced SDT/CDT/chemotherapy through promoting oxidative stress and overcoming the multidrug resistance. The mZMD decomposes under both ultrasound (US) irradiation and specific reactions in the tumor microenvironment (TME). The mZM composite structure reduces the recombination rate of e- and h+ to improve SDT. MnO2 not only oxidizes glutathione in tumor cells to enhance oxidative stress, but also converts the endogenic H2 O2 into O2 to improve the hypoxic TME, which enhances the effects of chemotherapy/SDT. Meanwhile, the generated Mn2+ catalyzes the endogenic H2 O2 into ·OH for CDT, and acts as magnetic resonance imaging agent to guide therapy. In addition, dissociated Zn2+ further breaks the redox balance of TME, and co-inhibits the expression of P-glycoprotein (P-gp) with generated ROS to overcome drug resistance. Thus, the as-prepared intelligent biodegradable mZMD provides an innovative strategy to enhance SDT/CDT/chemotherapy.


Assuntos
Compostos de Manganês , Óxidos , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Estresse Oxidativo , Óxidos/química , Microambiente Tumoral
16.
APMIS ; 130(3): 181-192, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34978741

RESUMO

Mycobacterium tuberculosis (M. tuberculosis) Rv1002c encodes the protein O-mannosyltransferase (PMT), which catalyzes the transfer of mannose to serine or threonine residues of proteins. We explored the function of PMT in vitro and in vivo. Rv1002c protein was heterogeneously overexpressed in nonpathogenic Mycobacterium smegmatis (named as MS_Rv1002c). A series of trials including mass spectrometry, transmission electron microscope, biofilm formation and antibiotics susceptibility were performed to explore the function of PMT on bacterial survival in vitro. Mouse experiments were carried out to evaluate the virulence of PMT in vivo. PMT decreased the cell envelope permeability and promoted microbial biofilm formation. PMT enhanced the mycobacterial survival in vivo and inhibited the release of pro-inflammatory cytokines in serum. The function might be associated with an increased abundance of some mannoproteins in culture filtrate (CF). PMT is likely to be involved in mycobacterial survival both in vivo and in vitro due to increasing the mannoproteins abundance in CF.


Assuntos
Biofilmes/crescimento & desenvolvimento , Permeabilidade da Membrana Celular/fisiologia , Manosiltransferases/metabolismo , Mycobacterium tuberculosis/patogenicidade , Animais , Proteínas de Bactérias/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Inflamação/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium smegmatis/metabolismo , Mycobacterium tuberculosis/metabolismo , Permeabilidade , Virulência/fisiologia
17.
J Mater Chem B ; 10(4): 637-645, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-34991154

RESUMO

Chemodynamic therapy (CDT) is an emerging approach to treat cancer based on the tumor microenvironment (TME), but its limited content of endogenous hydrogen peroxide (H2O2) weakens the anticancer effects. Herein, a multifunctional biomimetic nanozyme (Se@SiO2-Mn@Au/DOX, named as SSMA/DOX) is fabricated, which undergoes TME responsive self-cascade catalysis to facilitate MRI guided enhanced chemo/chemodynamic therapy. The SSMA/DOX nanocomposites (NCs) responsively degrade in acidic conditions of tumor to release Se, DOX, Au and Mn2+. Mn2+ not only enables MRI to guided therapy, but also catalyzes the endogenous H2O2 into hydroxyl radical (˙OH) for CDT. In addition, the Au NPs continuously catalyze glucose to generate H2O2, enhancing CDT by supplementing a sufficiently reactive material and cutting off the energy supply of the tumor by consuming glucose. Simultaneously, Se enhances the chemotherapy of doxorubicin hydrochloride (DOX) and CDT by upregulating ROS in the tumor cells, achieving remarkable inhibition effect towards tumor. Moreover, SSMA/DOX NCs have good biocompatibility and degradability, which avoid long-term toxicity and side effects. Overall, the degradable SSMA/DOX NCs provide an innovative strategy for tumor microenvironment responsive self-cascade catalysis to enhance tumor therapy.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Terapia Fototérmica , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Catálise , Linhagem Celular , Doxorrubicina/química , Feminino , Ouro/química , Ouro/farmacologia , Humanos , Manganês/química , Manganês/farmacologia , Teste de Materiais , Ratos , Ratos Sprague-Dawley , Selênio/química , Selênio/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Microambiente Tumoral/efeitos dos fármacos
18.
J Colloid Interface Sci ; 608(Pt 1): 344-354, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34626980

RESUMO

Prussian blue (PB) is a safe photothermal agent for tumor therapy, yet poor photothermal effect and single therapeutic function severely restrict its further clinical applications. Herein, a biodegradable "Nano-donut" (CMPB-MoS2-PEG) is fabricated for magnetic resonance (MR) imaging and enhanced photothermal therapy (PTT)/ chemodynamic therapy (CDT)/chemotherapy through responsive catalysis in tumor microenvironment (TME). The "Nano-donut" is organically composed of Cu/Mn ions doped-PB and MoS2. The porous donut structure of CMPB-MoS2-PEG endows them as a carrier for delivery of doxorubicin hydrochloride (DOX) to tumor site. The framework of Nano-donut specifically decomposes in TME due to the reaction between Fe2+/Fe3+ and H2O2. The multivalent elements (Cu/Fe/Mn ions) decrease the bandgap and then enhance CDT by synergistically catalyzing H2O2 into toxic ·OH. Meanwhile, the Mn4+ also reacts with H2O2 to generate O2, improving the hypoxia of TME and enhancing the chemotherapy effect of released DOX. The MoS2 mingles in the PB, which significantly enhances photothermal conversion efficiency (η) effect of PB from 16.02% to 38.0%. In addition, Fe3+ as T2-weighted MR imaging agent can achieve MR imaging-guided therapy. The data clearly shows Nano-donut/DOX nanocomposites (NCs) have a remarkable inhibition for cancer cells and excellent biological safety in tumor treatment.


Assuntos
Nanopartículas , Microambiente Tumoral , Catálise , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Peróxido de Hidrogênio , Imageamento por Ressonância Magnética , Terapia Fototérmica
19.
Adv Mater ; 34(25): e2104078, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34423476

RESUMO

Simple and rapid Young's modulus measurements of soft materials adaptable to various scenarios are of general significance, and they require miniaturized measurement platforms with easy operation. Despite the advances made in portable and wearable approaches, acquiring and analyzing multiple or complicated signals necessitate tethered bulky components and careful preparation. Here, a new methodology based on a self-locked stretchable strain sensor to haptically quantify Young's modulus of soft materials (kPa-MPa) rapidly is reported. The method demonstrates a fingertip measurement platform, which endows a prosthetic finger with human-comparable haptic behaviors and skills on elasticity sensing without activity constraints. A universal strategy is offered toward ultraconvenient and high-efficient Young's modulus measurements with wide adaptability to various fields for unprecedented applications.


Assuntos
Técnicas de Imagem por Elasticidade , Módulo de Elasticidade , Elasticidade , Técnicas de Imagem por Elasticidade/métodos , Humanos
20.
Nanomedicine (Lond) ; 16(26): 2343-2361, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34523352

RESUMO

Background: Radiosensitizers that can effectively consume glutathione provide broad prospects for enhancing the efficacy and reducing the side effects of radiotherapy. Aim: To explore the potential role of CuS@mSiO2@MnO2 nanocomposites in synergetic chemoradiotherapy. Methods: Nanocomposites were characterized by transmission electron microscopy, UV-Vis spectrometry and dynamic light scattering and were loaded with doxorubicin (DOX). The uptake and biodistribution of nanocomposites were observed by CCK8 assay, MRI and confocal laser scanning microscopy. The radiosensitization effect of nanocomposites and nanocomposites/DOX was assessed both in vitro and in vivo. Results:In vitro application of nanocomposites, with an average diameter of 30 nm and ζ-potential of 13.2 ± 0.4 mV, in combination with radiotherapy, depleted glutathione and induced ferroptosis and apoptosis. Nanocomposites/DOX exhibited tumor cell damage in vivo. Conclusion: We propose that this glutathione-depleting nanosystem could be a radiosensitizer as well as a drug transporter.


Assuntos
Ferroptose , Compostos de Manganês , Apoptose , Quimiorradioterapia , Doxorrubicina , Óxidos , Distribuição Tecidual
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