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1.
J Nanobiotechnology ; 22(1): 372, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918811

RESUMO

Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.


Assuntos
Bleomicina , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Hemangioma , Ácido Hialurônico , Agulhas , Poliésteres , Bleomicina/farmacologia , Animais , Camundongos , Coelhos , Hemangioma/tratamento farmacológico , Ácido Hialurônico/química , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Poliésteres/química , Humanos , Microesferas , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Liberação Controlada de Fármacos
2.
Qual Manag Health Care ; 33(3): 160-165, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38941582

RESUMO

OBJECTIVES: The purpose of this research was to assess the effect of telehealth management via WeChat on improving the quality of life of patients after percutaneous coronary intervention (PCI). METHODS: In this study, we retrospectively collected the clinical data of 118 patients who underwent PCI and received remote health management from our hospital via WeChat from June 2021 to September 2021 (WeChat group). The clinical data of 114 patients who underwent PCI but did not receive remote health management from our hospital from September 2020 to December 2020 were also collected (conventional group). Anxiety, depression, and quality of life scale scores were compared between the 2 groups at 6 months postdischarge. RESULTS: Six months postdischarge, patients in the WeChat group had significantly lower Self-rating Anxiety Scale (SAS) (55.7 ± 7.2 vs 58.8 ± 6.4, P = .001) and Self-rating Depression Scale (SDS) (56.0 ± 5.9 vs 58.2 ± 6.2, P = .007) scores than did those in the conventional group. Compared to those in the conventional group, the patients in the WeChat group had significantly greater 6 months post-discharge The World Health Organization Quality of Life - BREF scores in the following domains: physical (14.3 ± 1.7 vs 13.1 ± 1.7, P < .001 psychological (15.2 ± 1.3 vs 13.5 ± 1.5, P < .001 social relationship (12.9 ± 1.7 vs 12.3 ± 1.8, P = .01) and environmental (12.7 ± 2.0 vs 12.0 ± 1.9, P = .006). CONCLUSION: The use of WeChat to carry out remote health management for patients who underwent PCI can be an effective way to provide high-quality hospital medical services to patients' families and can effectively alleviate patients' anxiety and depression and enhance their quality of life.


Assuntos
Ansiedade , Depressão , Intervenção Coronária Percutânea , Qualidade de Vida , Telemedicina , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso
3.
Heliyon ; 10(5): e26649, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449654

RESUMO

Aims: The aim of our project was to identify proteins associated with the extent of spinal cord injury (SCI) and subsequent long-term neurological recovery. Methods: Through proteomic analysis, we identified proteins that are differentially expressed specifically in the acute phase of injury. We analyzed the concentrations of differentially expressed proteins in serum and the injured spinal cord segment by ELISA. Results: Serpina3n protein expression in the injured spinal cord segment was increased 101-fold at 12 h after severe SCI and 89-fold at 12 h after mild SCI, as determined by LC‒MS/MS. In the mild and severe SCI groups, serum Serpina3n levels began to increase at 12 h and peaked at 24 h. At 12 h, 24 h and 3 d after injury, serum Serpina3n protein levels were significantly correlated with the severity of injury (12 h: r = 0.6034, P = 0.008; 24 h: r = 0.7542, P = 0.0003; 3 d: r = 0.862, P < 0.001). Serum Serpina3n levels at 2 h, 24 h and 3 d post injury were significantly correlated with long-term neurological recovery at 28 d after SCI (2 h: r = -0.5781, P = 0.012; 24 h: r = -0.5912, P = 0.0098; 3 d: r = -0.7792, P < 0.0001). Methylprednisolone treatment would decrease the serum Serpina3n levels in mice with mild and severe SCI compared with those in placebo-group mice at 12 h and 24 h after SCI. The serum Serpina3n concentration in the severe SCI group was significantly reduced on the third day after steroid treatment. Conclusion: Taken together, these data suggest that serpina3n may be a circulating biomarker of acute SCI and may be closely associated with injury severity and long-term motor function recovery.

4.
J Matern Fetal Neonatal Med ; 37(1): 2301831, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38311547

RESUMO

OBJECTIVE: Copy number variations (CNVs) detected by high-resolution single nucleotide polymorphism microarrays (SNP arrays) have been associated with congenital heart defects (CHDs). The genetic mechanism underlying the development of CHDs remains unclear. METHODS: High-resolution SNP arrays were used to detect CNVs and traditional chromosomal analyses, respectively, were carried out on 60 and 249 fetuses from gestational 12-37 weeks old, having isolated or complex CHDs that were diagnosed using prenatal ultrasound. RESULTS: Twenty of the 60 fetuses (33.5%) had abnormalities, of which 23 CNVs (12 pathogenic, five probable pathogenic and six of undetermined significance) were detected by SNP arrays, and two distinct CNVs were present in three of these fetuses. In addition, in 39 patients with isolated congenital heart disease who had normal karyotypes, abnormal CNVs were present in 28.2% (11/39), and in patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. In patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. CONCLUSIONS: In conclusion, genome-wide high-resolution SNP array can improve the diagnostic rate and uncover additional pathogenic CNVs. The submicroscopic deletions and duplications of Online Mendelian Inheritance in Man (OMIM) genes found in this study have haploinsufficient (deletion) or triplosensitive (duplication) traits, which further clarify the etiology and inheritance of CHDs.


Assuntos
Doença da Artéria Coronariana , Cardiopatias Congênitas , Gravidez , Feminino , Humanos , Variações do Número de Cópias de DNA , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Análise em Microsséries , Cariótipo Anormal , Aberrações Cromossômicas , Polimorfismo de Nucleotídeo Único , Diagnóstico Pré-Natal
6.
ACS Nano ; 17(18): 17858-17872, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37656882

RESUMO

Replicating the controlled nanofibrillar architecture of collagenous tissue represents a promising approach in the design of tendon replacements that have tissue-mimicking biomechanics─outstanding mechanical strength and toughness, defect tolerance, and fatigue and fracture resistance. Guided by this principle, a fibrous artificial tendon (FAT) was constructed in the present study using an engineering strategy inspired by the fibrillation of a naturally spun silk protein. This bioinspired FAT featured a highly ordered molecular and nanofibrillar architecture similar to that of soft collagenous tissue, which exhibited the mechanical and fracture characteristics of tendons. Such similarities provided the motivation to investigate FAT for applications in Achilles tendon defect repair. In vitro cellular morphology and expression of tendon-related genes in cell culture and in vivo modeling of tendon injury clearly revealed that the highly oriented nanofibrils in the FAT substantially promoted the expression of tendon-related genes combined with the Achilles tendon structure and function. These results provide confidence about the potential clinical applications of the FAT.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Regeneração , Tendões , Seda/química
7.
Brain Res ; 1817: 148495, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37481153

RESUMO

BACKGROUND: White matter injury (WMI) is an important type of preterm brain injury, which may result in severe neurological sequelae and lack of effective treatments. It is ascertained that selective vulnerability of oligodendrocytes is closely related to the WMI in preterm infants. But the alteration of the endogenous oligodendrogenesis over long time after hypoxic-ischemic WMI is still not clearly elucidated. METHODS: We adopted an animal model of hypoxic-ischemic WMI in 3-day-old neonatal Sprague-Dawley rats. Immunofluorescence staining and western blotting were used to detect dynamic changes of oligodendrogenesis in the white matter region on postoperative day (POD) 1, 3, 7, 14, 28, 56 and 84. RESULTS: In the sham group, the oligodendrocyte lineage in the white matter reached a developmental peak from POD 3 to 14. The proliferation and development of oligodendrocyte precursor cells (OPCs) occurred primarily within POD 14. The number of mature oligodendrocytes showed an upward trend and a dynamic change in proliferation over time. While in the WMI group, the oligodendrocyte lineage was upregulated on POD1 and 3 but downregulated on POD 7 and 14. The proliferation of OPCs increased on POD 1 and decreased on POD 3 and 7, with the total number of OPCs significantly reduced from POD 3 to 14. The number of mature oligodendrocytes decreased from POD 3 to 28, and return to the level of the sham group on POD 56 and 84, whereas the MBP expression was still significantly downregulated on POD 56 and 84. CONCLUSIONS: Hypoxia-ischemia can have a long-term dynamic effect on the endogenous oligodendrogenesis of neonatal rat brain white matter. The proliferation of OPCs was promoted on POD 1 but inhibited from POD 3 to 14, which may be an early intervention target to improve oligodendrogenesis. The number of mature oligodendrocytes recover to the normal on POD 56 and 84 but the myelination is still blocked, which suggests it is essential to promote the maturation of oligodendrocyte and its function recovery at the same time within POD 28. Such efforts will provide the opportunity to test new interventions in pre-clinical studies for their promising clinical application.


Assuntos
Lesões Encefálicas , Substância Branca , Recém-Nascido , Humanos , Animais , Ratos , Animais Recém-Nascidos , Ratos Sprague-Dawley , Substância Branca/metabolismo , Recém-Nascido Prematuro , Hipóxia/metabolismo , Oligodendroglia/metabolismo , Lesões Encefálicas/metabolismo , Isquemia/metabolismo
8.
Neural Plast ; 2023: 4226139, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124874

RESUMO

Hypoxic-ischemic white matter injury (WMI) pathogenesis in preterm infants is not well established, and iron-related proteins in the brain may play an important role in imbalanced iron metabolism. We aimed to investigate the iron-related protein changes in neonatal rats after hypoxia-ischemia (HI), clarify the role of iron-related proteins in hypoxic-ischemic WMI, and potentially provide a new target for the clinical treatment of hypoxic-ischemic WMI in preterm infants. We adopted a WMI animal model of bilateral common carotid artery electrocoagulation combined with hypoxia in neonatal 3-day-old Sprague-Dawley rats. We observed basic myelin protein (MBP) and iron-related protein expression in the brain (ferritin, transferrin receptor [TfR], and membrane iron transporter 1 [FPN1]) via Western blot and double immunofluorescence staining. The expression of MBP in the WMI group was significantly downregulated on postoperative days (PODs) 14, 28, and 56. Ferritin levels were significantly increased on PODs 3, 7, 14, and 28 and were most significant on POD 28, returning to the sham group level on POD 56. FPN1 levels were significantly increased on PODs 7, 28, and 56 and were still higher than those in the sham group on POD 56. TfR expression was significantly upregulated on PODs 1, 7, and 28 and returned to the sham group level on POD 56. Immunofluorescence staining showed that ferritin, TfR, and FPN1 were expressed in neurons, blood vessels, and oligodendrocytes in the cortex and corpus callosum on POD 28. Compared with the sham group, the immune-positive markers of three proteins in the WMI group were significantly increased. The expression of iron-related proteins in the brain (ferritin, FPN1, and TfR) showed spatiotemporal dynamic changes and may play an important role in hypoxic-ischemic WMI.


Assuntos
Lesões Encefálicas , Ferritinas , Hipóxia-Isquemia Encefálica , Animais , Humanos , Recém-Nascido , Ratos , Animais Recém-Nascidos , Encéfalo/metabolismo , Ferritinas/metabolismo , Hipóxia , Hipóxia-Isquemia Encefálica/metabolismo , Recém-Nascido Prematuro , Ferro/metabolismo , Isquemia , Ratos Sprague-Dawley
9.
Mater Today Bio ; 19: 100547, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36896415

RESUMO

Circadian rhythm (CR) disruption contributes to tumor initiation and progression, however the pharmacological targeting of circadian regulators reversely inhibits tumor growth. Precisely controlling CR in tumor cells is urgently required to investigate the exact role of CR interruption in tumor therapy. Herein, based on KL001, a small molecule that specifically interacts with the clock gene cryptochrome (CRY) functioning at disruption of CR, we fabricated a hollow MnO2 nanocapsule carrying KL001 and photosensitizer BODIPY with the modification of alendronate (ALD) on the surface (H-MnSiO/K&B-ALD) for osteosarcoma (OS) targeting. The H-MnSiO/K&B-ALD nanoparticles reduced the CR amplitude in OS cells without affecting cell proliferation. Furthermore, nanoparticles-controlled oxygen consumption by inhibiting mitochondrial respiration via CR disruption, thus partially overcoming the hypoxia limitation for photodynamic therapy (PDT) and significantly promoting PDT efficacy. An orthotopic OS model demonstrated that KL001 significantly enhanced the inhibitory effect of H-MnSiO/K&B-ALD nanoparticles on tumor growth after laser irradiation. CR disruption and oxygen level enhancement induced by H-MnSiO/K&B-ALD nanoparticles under laser irradiation were also confirmed in vivo. This discovery first demonstrated the potential of CR controlling for tumor PDT ablation and provided a promising strategy for overcoming tumor hypoxia.

10.
Respir Physiol Neurobiol ; 308: 103980, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36273780

RESUMO

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by intermittent and recurrent upper airway collapse during sleep that leads to chronic intermittent hypoxia (CIH). The genioglossus (GG) is the largest dilator muscle, which controls the upper airway and plays an important role in OSA pathology. Elucidating its genetic alterations may help identify potential targets for OSA. However, the genetic aspects of the GG in CIH mice remain unclear. Here, we have conducted an RNA sequencing (RNA-Seq) analysis to assess the differentially expressed genes (DEGs) in the GG between CIH mice and normoxia (NOR) mice. A total of 637 DEGs were identified to be dysregulated in CIH mice compared with control mice. Bioinformatics analysis showed that the DEGs were related to various physiological processes, such as the endogenous stimulus responses, cellular component organization and metabolic processes. Extracellular matrix (ECM)-receptor interaction was the top KEGG pathway in the environmental information processing category with high significance and large fold changes. From the gene weight distributions of collagen (Col)-related biological processes (BPs), we found several significant DEGs, such as Col1a1, Col1a2, Mmp2, Col3a1, Col5a1, Fmod, and Col5a2. A PPI network showed that Col1a1 was linked to ECM-receptor interactions, responses to reactive oxygen species (ROS) and Col-related BPs. It was verified in vivo and in vitro that hypoxia can induce excess ROS and reduce Col expression levels. Moreover, we found NAC can effectively scavenge ROS and restore collagen synthesis. These findings contribute to a better understanding of the mechanisms linking OSA and upper airway muscle injury and may help identify potential therapeutic targets.


Assuntos
Apneia Obstrutiva do Sono , Transcriptoma , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Hipóxia , Fibromodulina
11.
Bioact Mater ; 22: 1-17, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36203961

RESUMO

The electrical microenvironment plays an important role in bone repair. However, the underlying mechanism by which electrical stimulation (ES) promotes bone regeneration remains unclear, limiting the design of bone microenvironment-specific electroactive materials. Herein, by simple co-incubation in aqueous suspensions at physiological temperatures, biocompatible regenerated silk fibroin (RSF) is found to assemble into nanofibrils with a ß-sheet structure on MXene nanosheets, which has been reported to inhibit the restacking and oxidation of MXene. An electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone regeneration. This MXene/RSF hydrogel also acts as a piezoresistive pressure transducer, which can potentially be utilized to monitor the electrophysiological microenvironment. RNA sequencing is performed to explore the underlying mechanisms, which can activate Ca2+/CALM signaling in favor of the direct osteogenesis process. ES is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages, as well as stimulating the neogenesis and migration of endotheliocytes. Consistent improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES in vivo. Collectively, the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis, regulating immune microenvironment and neovascularization under ES, leading to re-establish electrical microenvironment for bone regeneration.

13.
Chinese Journal of School Health ; (12): 711-714, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-973963

RESUMO

Objective@#To investigate physical activity status and associated factors of middle school students in Ningxia in January 2023, and to provide references for the better development of physical activity among middle school students.@*Methods@#In February 1-7,2023, a convenient sampling method was used to select 6 593 middle school students in 5 prefectural cities of Ningxia. Online questionnaires were used to investigate physical activity and its influencing factors in the previous month.@*Results@#The detection rates of sedentary behavior, light physical activity, moderate physical activity and vigorous physical activity was 92.25%, 4.66%, 2.72% and 0.38%, respectively. Multivariate Logistic regression analysis showed that being female, older age, overweight, obesity, COVID-19 infection, low to moderate family support, low to moderate level knowledge of physical activity, insufficient physical activity skills, insufficient physical activity equipment, long distance (>2.5 km or above) were associated with less physical activity ( OR=1.22, 2.47, 1.89, 1.39, 2.32, 1.20, 2.61, 1.85, 1.45, 1.23, 1.26, 1.11, 2.05, 1.77, 1.14, 1.43, P <0.05).@*Conclusion@#The poor physical activity performance of middle school students in Ningxia is related to BMI, COVID-19 infection, physical activity knowledge and skills, distance from activity places, etc. The influencing factors should be actively controlled to promote students physical health.

14.
Chinese Journal of School Health ; (12): 594-598, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-972754

RESUMO

Objective@#To investigate the incidence and influencing factors of abnormal body posture among urban primary school students in Yinchuan City, and to provide evidence for the prevention and treatment of abnormal body posture.@*Methods@#A multi stage stratified cluster random sampling method was adopted to select 1 947 urban primary school students aged 7-12 years from 9 schools in Yinchuan City. Body Style(Model.S-8.0) instrument was used to screen abnormal body posture and questionnaire was designed to investigate related factors.@*Results@#The comprehensive body posture score of urban primary school students in Yinchuan City was(22.07±2.87), and the detection rate of abnormal posturing was 71.29%;which varied significantly by gender, age, body mass index (BMI)( χ 2=9.84, 13.47, 6.46, P <0.05). Specially, the rate of girls (73.54%) was higher than that of boys( 69.07 %); the abnormal rate of children aged 7-8(68.24%) was lower than that of 9-10(72.17%) and 11-12(73.54%); obese children (74.91%) was higher than that of overweight (72.64%) and normal weight children(70.28%). The high and low shoulders (40.73%), pelvis forward (39.39%) and X/O legs (38.57%) were the most common indicators of abnormal posture; the composition of the overall body posture abnormalities was higher in mild (54.32%) than moderate (37.82%) and severe (7.85%).Multivariate Logistic regression analysis showed that girls( OR =1.23), being older(9-10 years old OR =1.89, 11-12 years old OR = 2.48 ), overweight ( OR =1.39) and obesity( OR =2.34), occasionally participate in physical exercise ( OR =2.96), exercise duration <30 minutes daily ( OR =2.77), video duration ≥2 h daily ( OR =2.84), almost no dairy products ( OR =1.79), almost no food Fish consumption ( OR =1.77), almost no vegetables ( OR =2.14), drinking carbonated beverages daily ( OR =2.97), and sleeping time <6 h daily ( OR =2.56) were the related factors of body posture development of urban primary school students( P <0.05).@*Conclusion@#The abnormal body posture of urban primary school students in Yinchuan City is prevalent, which is related to the timely length of physical exercise, nutrition, video screen and sleep duration, and should be paid enough attention.

15.
Acta Pharmaceutica Sinica ; (12): 339-350, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-965704

RESUMO

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981736

RESUMO

OBJECTIVE@#To provide an overview of the incidence of knee donor -site morbidity after autologous osteochondral mosaicplasty.@*METHODS@#A comprehensive search was conducted in PubMed, EMbase, Wanfang Medical Network, and CNKI databases from January 2010 to April 20, 2021. Relevant literature was selected based on predefined inclusion and exclusion criteria, and data were evaluated and extracted. The correlation between the number and size of transplanted osteochondral columns and donor-site morbidity was analyzed.@*RESULTS@#A total of 13 literatures were included, comprising a total of 661 patients. Statistical analysis revealed an incidence of knee donor-site morbidity at 8.6% (57/661), with knee pain being the most common complaint, accounting for 4.2%(28/661). There was no significant correlation between the number of osteochondral columns and postoperative donor-site incidence (P=0.424, N=10), nor between the diameter size of osteochondral columns and postoperative donor-site incidence(P=0.699, N=7).@*CONCLUSION@#Autologous osteochondral mosaicplasty is associated with a considerable incidence of knee donor-site morbidity, with knee pain being the most frequent complaint. There is no apparent correlation between donor-site incidence and the number and size of transplanted osteochondral columns. Donors should be informed about the potential risks.


Assuntos
Humanos , Incidência , Cartilagem/transplante , Joelho , Articulação do Joelho/cirurgia , Dor , Cartilagem Articular , Transplante Autólogo , Transplante Ósseo
17.
J Chromatogr A ; 1681: 463443, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36088775

RESUMO

Benzophenone-type ultraviolet filters (BP-UVFs) are a group of emerging contaminants, which found in various environmental aqueous samples raising potential risks for public health concern and could bioaccumulate in the food chain. This study describes a simple and "green" method to rapidly analyze five BP-UVFs that are frequently found in surface water and in seawater samples. Dispersive solid-phase extraction (DSPE) using a zeolitic imidazolate framework­8 (ZIF-8) as the sorbent was applied to efficiently extract the BP-UVFs from aqueous samples, and they were then detected and quantified by UHPLC-electrospray ionization (+)-quadrupole time-of-flight mass spectrometry (UHPLC-ESI (+)-QTOF-MS). The ZIF-8 sorbent was synthesized by a green one-step mechanochemical process using water-assisted grinding and a stoichiometric reaction. The Box-Behnken Design coupled with the response surface method was applied to optimize the main DSPE extraction factors. The developed method was fully validated, showing low limits of quantification (LOQs; 0.3-20 ng L-1), satisfactory mean spiked recoveries (72-105%), and a high level of precision (3-9%). A preliminary analysis of the surface water and seawater samples revealed that 2-hydroxy-4-methoxybenzophenone (BP-3) was the most common BP-UVF present in our aquatic environment, likely due to its widespread applications and slow rate of degradation.


Assuntos
Poluentes Químicos da Água , Zeolitas , Benzofenonas/análise , Extração em Fase Sólida/métodos , Água , Poluentes Químicos da Água/análise , Zeolitas/química
19.
Adv Healthc Mater ; 11(20): e2200938, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35904523

RESUMO

Although immune checkpoint inhibitors (ICIs) have been widely applied to treat non-small cell lung cancer (NSCLC), a significant proportion of patients, especially those with spinal metastasis (NSCLC-SM), are insensitive to anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) ICIs. A drug delivery nano-controller of PD-L1 that targets NSCLC-SM can solve this problem, however, none have been developed to date. In this study, it is shown that integrin ß3 (ß3-int) is strongly upregulated in NSCLC-SM. Its inhibitor RGDyK promotes PD-L1 ubiquitination, indicating the potential application of RGDyK as a new PD-L1 inhibitor in nano-controller and a targeting peptide for NSCLC-SM treatment. According to the synergistic effect of photodynamic therapy and ICIs on T-cell activation through the release of tumor antigens, RGDyK-modified and zinc protoporphyrin (ZnPP)-loaded mesoporous silicon nanoparticles (ZnPP@MSN-RGDyK) are fabricated. The ZnPP@MSN-RGDyK nanoparticles precisely target ß3-int to inhibit PD-L1, exhibiting high photodynamic therapy efficiency, and excellent immunotherapeutic effects in an NSCLC-SM mouse model. Collectively, the findings indicate that ZnPP@MSN-RGDyK is a promising immunotherapeutic agent for treating NSCLC-SM.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias da Coluna Vertebral , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/uso terapêutico , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Integrina beta3/uso terapêutico , Silício , Neoplasias da Coluna Vertebral/tratamento farmacológico , Imunoterapia , Antígenos de Neoplasias/uso terapêutico
20.
Small ; 18(29): e2107787, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35751455

RESUMO

Low responsiveness to anti-programmed death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) for solid tumors indicates the presence of other immunosuppressive pathways. Siglec15, a newly discovered immune checkpoint, has been reported to repress immune responses in the tumor microenvironment (TME) and regulate osteoclast differentiation. However, the role of Siglec15 in the treatment for bone metastasis remains unclear. Herein, Siglec15 shows significantly higher expression in lung adenocarcinoma spinal metastasis (LUAD-SM) than in para-cancerous spinal tissues and primary LUAD. Subsequently, a TME-responsive hollow MnO2 nanoplatform (H-M) loaded with Siglec15 siRNA and cisplatin (H-M@siS15/Cis) is developed, and the surface is modified with an aspartic acid octapeptide (Asp8 ), thus allowing H-M to target spinal metastasis. High drug-loading capacity, good biocompatibility, effective tumor accumulation, and efficient Siglec15 silencing are demonstrated. Furthermore, the nanoparticles could reverse immunosuppression caused by tumor cells and tumor-associated macrophages (TAMs) and inhibit osteoclast differentiation via Siglec15 downregulation in vitro. In a LUAD-SM mouse model, H-M@siS15/Cis-Asp8 exhibits superior therapeutic efficacy via synergetic immunochemotherapy and osteolysis inhibition. Taken together, this single nanoplatform reveals the therapeutic potential of the new immune checkpoint Siglec15 in LUAD-SM and provides a strategy to treat this disease.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Osteólise , Neoplasias da Coluna Vertebral , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Compostos de Manganês , Camundongos , Osteólise/tratamento farmacológico , Óxidos , Neoplasias da Coluna Vertebral/tratamento farmacológico , Microambiente Tumoral
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