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1.
J Appl Toxicol ; 42(7): 1276-1286, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35102572

RESUMO

To investigate the neurotoxicity of pyrazinamide (PZA) to larval zebrafish, the PZA effects were assessed followed by its mechanism being explored. Same as isoniazid (INH), this compound is a first-line anti-tuberculosis drug and is suggested to be a risk that inducing nerve injury with long-term intoxication. Our findings indicated that zebrafish larvae obtained severe nerve damage secondary to constant immersion in various concentrations of PZA (i.e., 0.5, 1.0, and 1.5 mM) from 4 hpf (hours post fertilization) onwards until 120 hpf. The damage presented as dramatically decrease of locomotor capacity and dopaminergic neuron (DAN)-rich region length in addition to defect of brain blood vessels (BBVs). Moreover, PZA-administrated zebrafish showed a decreased dopamine (DA) level and downregulated expression of neurodevelopment-related genes, such as shha, mbp, neurog1, and gfap. However, secondary to 48-h restoration in fish medium (i.e., at 168 hpf), the neurotoxicity described above was prominently ameliorated. The results showed that PZA at the concentrations we tested was notably neurotoxic to larval zebrafish, and this nerve injury was restorable after PZA withdrawing. Therefore, this finding will probably provide a reference for clinical medication.


Assuntos
Pirazinamida , Peixe-Zebra , Animais , Antituberculosos/toxicidade , Isoniazida/toxicidade , Larva , Pirazinamida/toxicidade , Peixe-Zebra/metabolismo
2.
J Foot Ankle Surg ; 58(1): 171-175, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30448182

RESUMO

Polydactyly is a common congenital deformity of the foot that can be categorized as preaxial, central, or postaxial. Current treatments involve resecting the supernumerary toe(s) and repairing the normal toe(s) and soft tissue. Here, we present the first published report describing a very rare case of polydactyly of the foot, in which the supernumerary toe originated from a deformed calcaneus, which formed an abnormal bony bump. Preoperatively, 3-dimensional (3D) computed tomography reconstruction images revealed the morphology of the deformed toe and calcaneus, and gait analysis showed an abnormal weightbearing zone in the left foot. The 3D printing technology and a specially designed 3D-printed guiding plate were used for osteotomy. Postoperatively, x-ray showed that the calcaneus had a normal shape and surface, whereas gait analysis showed that the left foot was uniformly loaded and the area of pain was eliminated. Our findings should raise awareness among clinicians that a 3D-printed guiding plate is useful in the treatment of such an unusual deformity.


Assuntos
Placas Ósseas , Calcâneo/anormalidades , Dedos/anormalidades , Osteotomia , Polidactilia/cirurgia , Impressão Tridimensional , Dedos do Pé/anormalidades , Dedos/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Dedos do Pé/cirurgia
3.
Opt Express ; 26(10): 12903-12911, 2018 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-29801323

RESUMO

We propose and demonstrate a novel type of sampled Bragg gratings by combining a helically twisted fiber and a Bragg grating. A comb-like spectrum with a series of harmonic narrow resonances is observed, and the influence of geometrical parameters on the resonances is studied. As a special application, the intrinsic nature of the device that contains the Bragg grating and helical fiber spectral responses permits the temperature to be detected from the former, whereas the mechanical torsion is extracted from the latter, suggesting a potential for the simultaneous measurement of these two parameters. The proposed configuration features simplification, easy fabrication, high flexibility, stability, and low cost, and therefore has good prospects for sensor applications, as well as other applications, such as multi-channel filters, distributed Bragg reflectors, etc.

5.
Int J Med Sci ; 14(7): 690-697, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824302

RESUMO

The RANKL/RANK/OPG pathway plays an important role in regulating bone remodeling and bone turnover. However, the association of the genes variants with the risk of ONFH has rarely been reported. Here, we analyzed the correlation of the 10 SNPs polymorphisms of RANKL, RANK, OPG, TRAF6, and NFATC1 genes with the risk and development of ONFH in 200 ONFH patients and 177 health controls of Chinese population with using Mass ARRAY® platform. The results showed that the recessive model of NFATC1rs9518 was significantly associated with increased ONFH risk (OR:8.223, P=0.048); the proportion of stage Ⅳ patients in the rs9518TC genotype carriers was statistically higher than that of stage Ⅲ patients (P=0.03); in the T-C haplotype carriers of Naftac1, the proportion of bilateral hips lesions was also significantly enhanced than that of unilateral hip lesions(P=0.05). In addition, the proportion of idiopathic ONFH in the TT genotype carriers of OPGrs2073617 was significantly higher than that of steroid or alcohol-induced ONFH, respectively, while in the TC genotype carriers of the SNP, the proportion of idiopathic ONFH remarkably decreased compared with that of Alcohol-induced ONFH, P=0.021. Our results were first found that NFATC1rs9518 closely associated with the risk and the development of ONFH, while OPGrs2073617 statistically correlated with the etiological classification of ONFH.


Assuntos
Necrose da Cabeça do Fêmur/genética , Fatores de Transcrição NFATC/genética , Osteonecrose/genética , Osteoprotegerina/genética , Idoso , China , Feminino , Necrose da Cabeça do Fêmur/fisiopatologia , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética , Ligante RANK/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Transdução de Sinais/genética , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/genética
6.
Chem Commun (Camb) ; 60(42): 5558-5561, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38712611

RESUMO

A novel Catellani-type conversion is reported using aryl-thianthreniums (aryl-TTs) instead of aryl halides. Three classes of ortho-dual C-H functionalization involving alkylation, amination, and deuterated methylation and five types of ipso-operation including alkenylation, cyanation, methylation, hydrogenation, and alkynylation all proceed well in this procedure. In this conversion, aryl-TTs exhibit satisfactory reactivity and feature the advantage that the leaving TT unit can be recovered. More strikingly, this finding represents a new chemistry conversion of aryl-TTs, wherein contiguous tri-functionalization in a single chemical manipulation is realized.

7.
J Orthop Res ; 42(1): 66-77, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37291947

RESUMO

Osteoarthritis (OA), a late-stage complication of developmental dysplasia of the hip (DDH), is a key factor leading to further degeneration of joint function. Studies have shown that Sestrin2 (SESN2) is a positive regulator in protecting articular cartilage from degradation. However, the regulatory effects of SESN2 on DDH-OA and its upstream regulators remain obscure. Here, we first identified that the expression of SESN2 significantly decreased in the cartilage of DDH-OA samples, with an expression trend negatively correlated with OA severity. Using RNA sequencing, we identified that the upregulation of miR-34a-5p may be an important factor for the decrease in SESN2 expression. Further exploring the regulation mechanism of miR-34a-5p/SESN2 is of great significance for understanding the mechanism of DDH occurrence and development. Mechanistically, we showed that miR-34a-5p could significantly inhibit the expression of SESN2, thereby promoting the activity of the mTOR signaling pathway. We also found that miR-34a-5p significantly inhibited SESN2-induced autophagy, thereby suppressing the proliferation and migration of chondrocytes. We further validated that knocking down miR-34a-5p in vivo resulted in a significant increase in SESN2 expression and autophagy activity in DDH-OA cartilage. Our study suggests that miR-34a-5p is a negative regulator of DDH-OA, and may provide a new target for the prevention of DDH-OA.


Assuntos
Cartilagem Articular , Displasia do Desenvolvimento do Quadril , MicroRNAs , Osteoartrite do Quadril , Humanos , MicroRNAs/metabolismo , Displasia do Desenvolvimento do Quadril/metabolismo , Condrócitos/metabolismo , Cartilagem Articular/metabolismo , Osteoartrite do Quadril/metabolismo , Autofagia/genética , Apoptose , Sestrinas/metabolismo
8.
Joint Bone Spine ; 91(2): 105669, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38042362

RESUMO

OBJECTIVE: Disorders of bone homeostasis are the key factors leading to metabolic bone disease, such as senile osteoporosis, which is characterized by age-related bone loss. Bone marrow stromal cells (BMSCs) possess high osteogenic capacity which has been regarded as a practical approach to preventing bone loss. Previous studies have shown that the osteogenic differentiation ability of BMSCs is significantly decreased in senile osteoporosis. Recently, circular RNAs (circRNAs) have been regarded as critical regulators in controlling the osteogenic differentiation of BMSCs by sponging microRNAs (miRNAs). Our study aimed to discover new and critical osteogenesis-related circRNAs that can promote bone formation in senile osteoporosis. METHODS: We detected the dysregulated circRNAs of BMSCs upon osteogenic differentiation induction and identified the critical osteogenic circRNA (circ-3626). The relationship between circ-3626 and osteoporosis was further verified in clinical bone samples and aged mice by qPCR. Moreover, circ-3626 AAV was constructed to examine the osteogenic effect of circ-3626 on bone formation via using Micro-CT, double calcein labeling, and the three-point bending tests. Bioinformatics analysis, Luciferase report gene assays, FISH, RNA pull-down, qPCR, Western Blots, and alizarin red staining assay explore the effects and mechanisms of circ-3626 on osteogenic differentiation of BMSCs. RESULTS: Circ-3626 was identified as a pivotal osteogenesis-related circRNA via RNA sequencing. The results of alizarin red staining, Western blots, and qPCR assays suggest that overexpressing circ-3626 dramatically accelerates the osteogenic capability of BMSCs. Furthermore, the bone repair capability of aging mice could be significantly improved by circ-3626 AAV treatment. Micro RNA miR-338-3p was identified as the downstream target of circ-3626. Overexpression of circ-3626 increases the expression of Runx2 by sponging miR-338-3p, thereby promoting the osteogenic differentiation of BMSCs by upregulating the expression of osteogenic genes. In addition, Western blots, and qPCR assays suggest circ-3626 AAV treatment promote the expression of Runx2 and osteogenic marker genes. CONCLUSION: Thus, we demonstrate that circ-3626 plays a pivotal role in promoting bone formation through the miR-338-3p/Runx2 axis and may provide new strategies for preventing and treating the bone loss of senile osteoporosis.


Assuntos
Antraquinonas , MicroRNAs , Osteoporose , Humanos , Camundongos , Animais , Osteogênese/genética , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoporose/genética , Diferenciação Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética
9.
J Orthop Res ; 42(6): 1244-1253, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38151824

RESUMO

Postmenopausal osteoporosis (PMOP) affects hundreds of millions of elderly women worldwide. The imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption is the key factor in the progression of PMOP. Recently, exosomal circular RNAs have been considered as critical regulators in physiological and pathological progress. However, their roles in PMOP still require further exploration. Herein, we identified that the expression of exosomal circFAM63B significantly increased in PMOP patients and is closely related to bone density. We further demonstrated that circFAM63B inhibits osteogenic differentiation of bone marrow stromal cells and bone formation in ovariectomy mice by using a combination of in vitro and in vivo experiment strategies. Mechanistically, circFAM63B promotes HMGA2 expression by inhibiting miR-578, thereby suppressing bone repair. Our study proved that exosomal circFAM63B suppresses the bone regeneration of PMOP by regulating the miR-578/HMGA2 axis, which may provide new insights into the pathogenesis and development of PMOP. Knocking down exosomal circFAM63B could be regarded as a new strategy for the treatment of PMOP.


Assuntos
Regeneração Óssea , Exossomos , Proteína HMGA2 , MicroRNAs , Osteoporose Pós-Menopausa , RNA Circular , MicroRNAs/metabolismo , MicroRNAs/genética , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/genética , Feminino , Proteína HMGA2/metabolismo , Proteína HMGA2/genética , Animais , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Exossomos/metabolismo , Camundongos , Pessoa de Meia-Idade , Osteogênese , Idoso , Camundongos Endogâmicos C57BL
10.
Front Bioeng Biotechnol ; 11: 1111866, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36970621

RESUMO

Early, efficient and sensitive detection of serum markers in cervical cancer is very important for the treatment and prognosis to cervical cancer patients. In this paper, a SERS platform based on surface enhanced Raman scattering technology was proposed to quantitatively detect superoxide dismutase in serum of cervical cancer patients. Au-Ag nanoboxs array was made by oil-water interface self-assembly method as the trapping substrate. The single-layer Au-AgNBs array was verified by SERS for possessing excellent uniformity, selectivity and reproducibility. 4-aminothiophenol (4-ATP) was used as Raman signal molecule, it will be oxidized to dithiol azobenzene under the surface catalytic reaction with the condition of PH = 9 and laser irradiation. The quantitative detection of SOD could be achieved by calculating the change of characteristic peak ratio. When the concentration was from 10 U mL-1-160 U mL-1, the concentration of SOD could be accurately and quantitatively detected in human serum. The whole test was completed within 20 min and the limit of quantitation was 10 U mL-1. In addition, serum samples from the cervical cancer, the cervical intraepithelial neoplasia and healthy people were tested by the platform and the results were consistent with those of ELISA. The platform has great potential as a tool for early clinical screening of cervical cancer in the future.

11.
Front Bioeng Biotechnol ; 11: 1209752, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465690

RESUMO

Introducing bone regeneration-promoting factors into scaffold materials to improve the bone induction property is crucial in the fields of bone tissue engineering and regenerative medicine. This study aimed to develop a Sr-HA/PTH1-34-loaded composite hydrogel system with high biocompatibility. Teriparatide (PTH1-34) capable of promoting bone regeneration was selected as the bioactive factor. Strontium-substituted hydroxyapatite (Sr-HA) was introduced into the system to absorb PTH1-34 to promote the bioactivity and delay the release cycle. PTH1-34-loaded Sr-HA was then mixed with the precursor solution of the hydrogel to prepare the composite hydrogel as bone-repairing material with good biocompatibility and high mechanical strength. The experiments showed that Sr-HA absorbed PTH1-34 and achieved the slow and effective release of PTH1-34. In vitro biological experiments showed that the Sr-HA/PTH1-34-loaded hydrogel system had high biocompatibility, allowing the good growth of cells on the surface. The measurement of alkaline phosphatase activity and osteogenesis gene expression demonstrated that this composite system could promote the differentiation of MC3T3-E1 cells into osteoblasts. In addition, the in vivo cranial bone defect repair experiment confirmed that this composite hydrogel could promote the regeneration of new bones. In summary, Sr-HA/PTH1-34 composite hydrogel is a highly promising bone repair material.

12.
Drug Des Devel Ther ; 17: 597-612, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36866196

RESUMO

Background: Atherosclerosis (AS) is an immunoinflammatory disease associated with dyslipidemia. Zhuyu Pill (ZYP) is a classic Chinese herbal compound that has been shown to exhibit anti-inflammatory and lipid-lowering effects on AS in our previous studies. However, the underlying mechanisms by which ZYP ameliorates atherosclerosis have not yet been fully investigated. In this study, network pharmacology and in vivo experiments were conducted to explore the underlying pharmacological mechanisms of ZYP on ameliorating AS. Methods: The active ingredients of ZYP were acquired from our previous study. The putative targets of ZYP relevant to AS were obtained from TCMSP, SwissTargetPrediction, STITCH, DisGeNET, and GeneCards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore, in vivo experiments were carried out for target validation in apolipoprotein E (ApoE) -/- mice. Results: Animal experiments revealed that ZYP ameliorated AS mainly through lowering blood lipids, alleviating vascular inflammation, and decreasing the levels of vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), monocyte chemotactic protein-1 (MCP-1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, the results of Real-Time quantitative PCR revealed that ZYP inhibited the gene expressions of mitogen-activated protein kinase (MAPK) p38, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) p65. The Immunohistochemistry and Western blot assays showed the inhibitory effect of ZYP on the proteins level of p38, p-p38, p65, and p-p65. Conclusion: This study has provided valuable evidence on the pharmacological mechanisms of action of ZYP in ameliorating AS that will be useful for forming the rationale of future research studying the cardio-protection and anti-inflammation effects of ZYP.


Assuntos
Aterosclerose , Medicamentos de Ervas Chinesas , Farmacologia em Rede , Animais , Humanos , Camundongos , Aterosclerose/tratamento farmacológico , Western Blotting , Fator de Necrose Tumoral alfa , Medicamentos de Ervas Chinesas/uso terapêutico
13.
Anal Chim Acta ; 1247: 340890, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36781256

RESUMO

In this paper, a multiplex signal amplification strategy was developed for the determination of miR-214 and miR-221 on a surface-enhanced Raman scattering (SERS)-enabled lab-on-a-chip (LoC) system to realize the early-stage diagnosis of Parkinson's disease (PD). The gold nanobipyramids (GNBPs) with great monodispersity were functionalized with Raman reporter molecules and hairpin DNA 1, serving as the SERS nanotags. The presence of targets can initial the strand displacement amplification (SDA) reaction and the numerous short-stranded trigger DNA (tDNA) can be released under the action of polymerase and nicking enzyme. Then, the tDNA can trigger the catalytic hairpin assembly (CHA) event between the SERS nanotags and the capture nanoprobes (Magnetic beads (MBs) modified with hairpin DNA 2), resulting in the aggregation of GNBPs on the MBs surface. The multiplex signal amplification contributed by the SDA-CHA strategy and the magnet-induced aggregation effect can ultimately lead to the significant improvement of the detection sensitivity and the limit of detection (LOD) was low to aM level with reproducibility and specificity meanwhile. Furthermore, a MPTP-induced PD mice model was established to verify the practicability and the expression level of miR-214 and miR-221 at different stages analyzed with the LoC system was confirmed by qRT-PCR.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , MicroRNAs , Doença de Parkinson , Animais , Camundongos , Reprodutibilidade dos Testes , Doença de Parkinson/diagnóstico , DNA , Técnicas de Amplificação de Ácido Nucleico/métodos , Análise Espectral Raman/métodos , Limite de Detecção , Ouro , MicroRNAs/genética , MicroRNAs/análise , Técnicas Biossensoriais/métodos
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 302: 123088, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37392535

RESUMO

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder with significant economic and societal impacts, whereas early AD diagnosis remains a considerable challenge. Here, a robust and convenient surface-enhanced Raman scattering (SERS) analysis platform was fabricated on a microarray chip to dissect the variation in serum composition for AD diagnosis, eliminating the invasive cerebrospinal fluid (CSF)-based and costly instrument-dependent diagnostic methods. AuNOs array prepared by self-assembly at liquid-liquid interface enabled the acquirement of SERS spectra with excellent reproducibility. Moreover, a finite-difference time-domain (FDTD) simulation suggested the significant plasmon hybridization generated by AuNOs aggregation, resulting in high signal-to-noise ratio SERS spectra. We established an AD mice model with Aß1-40 induction followed by recording the serum SERS spectra at different stages. A multivariate analysis method of principal component analysis (PCA)-weighted representation-based k-nearest neighbor (WRKNN) was applied for the characteristics extraction to improve the classification performance, with an accuracy of over 95 %, an AUC of over 90 %, a sensitivity of over 80 %, and a specificity of over 96.7 %. The results of this study demonstrate the potential of SERS application as a diagnostic screening method, following further validation and optimization, which may open up new exciting opportunities for future biomedical applications.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Análise de Componente Principal , Reprodutibilidade dos Testes , Análise Multivariada , Análise por Conglomerados , Análise Espectral Raman/métodos
15.
Chin Herb Med ; 15(1): 94-101, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36875428

RESUMO

Objective: Chronic inflammation plays a fatal role in tumor metastasis. Pterostilbene (PTE) is a natural dimethylated analogue of resveratrol with anticancer and anti-inflammatory activities. This study aimed to investigate the inhibitory effect of PTE on inflammation-associated metastasis and explore the underlying mechanisms. Methods: Lipopolysaccharide (LPS)-induced lung inflammation and melanoma metastasis models were established in mice. After PTE treatment for four weeks, the organ index, histological changes, proinflammatory cytokines, and the expression and activity of neutrophil elastase (NE), a biomarker of neutrophil influx in the lungs, were analysed. Additionally, direct effects of PTE on NE-induced B16 cell migration were explored in wound healing and Transwell assays, and the expression of thrombospondin-1 (TSP-1) and epithelial-mesenchymal transition (EMT) markers were also detected. Results: PTE obviously attenuated the LPS-induced metastasis of circulatory B16 cells to lungs by reducing the number of metastatic nodules on the lung surfaces and the lung weight/body weight ratio. PTE treatment also significantly reduced LPS-activated increase levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the lungs of tumor-bearing mice. In addition, increased expression and enzyme activity of NE and decreased expression of TSP-1 were observed, and these were blocked by PTE. In vitro, PTE at concentrations without cytotoxicity also markedly suppressed NE-triggered B16 cell migration, prevented NE-induced TSP-1 proteolysis and reversed the expression of vimentin, N-cadherin and E-cadherin. Conclusion: PTE could block inflammation-enhanced tumor metastasis, and the underlying mechanism might be associated with the inhibition of NE-mediated TSP-1 degradation.

16.
Anal Chim Acta ; 1254: 341113, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37005023

RESUMO

Cisplatin has been widely applied in the clinical treatment of various cancers, whereas liver injury induced by its hepatotoxicity is still a severe issue. Reliable identification of early-stage cisplatin-induced liver injury (CILI) can improve clinical care and help to streamline drug development. Traditional methods, however, cannot achieve enough information at the subcellular level due to the requirement of the labeling process and low sensitivity. To overcome these, we designed an Au-coated Si nanocone array (Au/SiNCA) to fabricate the microporous chip as the surface-enhanced Raman scattering (SERS) analysis platform for the early diagnosis of CILI. A CILI rat model was established, and the exosome spectra were obtained. The principal component analysis (PCA)-representation coefficient-based k-nearest centroid neighbor (RCKNCN) classification algorithm was proposed as the multivariate analysis method to build the diagnosis and staging model. The PCA-RCKNCN model has been validated to achieve a satisfactory result, with accuracy and AUC of over 97.5%, and sensitivity and specificity of over 95%, indicating that SERS combined with the PCA-RCKNCN analysis platform can be a promising tool for clinical applications.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Nanopartículas Metálicas , Animais , Ratos , Cisplatino/toxicidade , Detecção Precoce de Câncer , Aprendizado de Máquina , Análise Espectral Raman/métodos , Nanopartículas Metálicas/toxicidade
17.
J Bone Miner Res ; 38(7): 1015-1031, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37129025

RESUMO

Dysregulation of bone homeostasis is closely related to the pathogenesis of osteoporosis. Suppressing bone resorption by osteoclasts to attenuate bone loss has been widely investigated, but far less effort has been poured toward promoting bone formation by osteoblasts. Here, we aimed to explore magnesium ascorbyl phosphate (MAP), a hydrophilic and stable ascorbic acid derivative, as a potential treatment option for bone loss disorder by boosting osteoblastogenesis and bone formation. We found that MAP could promote the proliferation and osteoblastic differentiation of human skeletal stem and progenitor cells (SSPCs) in vitro. Moreover, MAP supplementation by gavage could alleviate bone loss and accelerate bone defect healing through promoting bone formation. Mechanistically, we identified calcium/calmodulin-dependent serine/threonine kinase IIα (CaMKIIα) as the target of MAP, which was found to be directly bound and activated by MAP, then with a concomitant activation in the phosphorylation of ERK1/2 (extracellular regulated kinase 1/2) and CREB (cAMP-response element binding protein) as well as an elevation of C-FOS expression. Further, blocking CaMKII signaling notably abolished these effects of MAP on SSPCs and bone remodeling. Taken together, our data indicated that MAP played an important role in enhancing bone formation through the activation of CaMKII/ERK1/2/CREB/C-FOS signaling pathway and may be used as a novel therapeutic option for bone loss disorders such as osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Osteoporose , Humanos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/uso terapêutico , Osteogênese , Transdução de Sinais , Diferenciação Celular , Sistema de Sinalização das MAP Quinases , Osteoblastos/metabolismo , Osteoporose/metabolismo
18.
Front Bioeng Biotechnol ; 10: 1124441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36714617

RESUMO

Telomerase has been considered as a biomarker for early diagnosis and prognosis assessment of hepatocellular carcinoma (HCC), while the highly sensitive and specific methods remain challenging. To detect telomerase, a novel surface-enhanced Raman scattering (SERS) biosensor was constructed using the dual DNA-catalyzed amplification strategy composed of strand displacement amplification (SDA) and catalytic hairpin assembly (CHA). This strategy relies on the extension reaction of telomerase primer induced by telomerase, forming long-stranded DNAs with repetitive sequence to catalyze the follow-up SDA event. Subsequently, the SDA products can trigger the CHA reaction between the SERS probes (Au-Ag nanocages (Au-AgNCs) modified with hairpin DNA1 and Raman reporters) and capture substrate (Au@SiO2 array labeled with hairpin DNA2), resulting in the formation of numerous "hot spots" to significantly enhance the SERS signal. Results are promising that the established biosensor presented excellent reproducibility, specificity and sensitivity. Moreover, ELISA was applied as the golden standard to verify the application of the proposed biosensor in real samples and the results confirmed the satisfactory accuracy of our method. Therefore, the proposed SERS biosensor has the potential to be an ideal tool for the early screening of HCC.

19.
ACS Appl Mater Interfaces ; 14(12): 14253-14263, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35306808

RESUMO

Sodium-ion batteries (SIBs) are on the verge of achieving practical applications, and the key is to find suitable electrode materials. The polyanionic iron-based material Na3.12Fe2.44(P2O7)2 (NFPO) possesses an open three-dimensional framework structure with good thermal stability and is regarded as an outstanding cathode material for SIBs. Nevertheless, its poor electrical conductivity, problems with erosion of electrolytes, and structural deterioration during cycling still need to be urgently addressed. Here, we first design a Mg2+-doped NFPO (NFPO-Mg) material with a dual-action effect. On the one hand, Mg2+ improves the intrinsic conductivity of the NFPO material, and on the other hand, Mg2+ promotes the formation of a homogeneous and stable cathode-electrolyte interphase film during the cycling process, which results in a superior rate performance and cycling stability. A capacity of 68.6 mAh g-1 was achieved at 50C (1C = 117.4 mAh g-1), and a capacity retention of 79.1% was maintained after 3000 cycles at 20C. More impressively, NFPO-Mg exhibits outstanding high-temperature electrochemical performance, with a capacity retention of 95.3% after 400 cycles at 10C at 60 °C (much higher than the 54.2% for the NFPO). This paper explores an effective method for improving the electrochemical performance of cathode materials, which may prove instrumental in guiding the design of more high-performance cathode materials in the future.

20.
Front Surg ; 9: 849679, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711699

RESUMO

Objective: The efficacy of hybrid (Dynesys and fusion) surgery and the traditional transforaminal lumbar interbody fusion surgery was compared in patients with multi-segmental lumbar spinal stenosis. Methods: A total of 68 patients with multi-segmental lumbar spinal stenosis subjected to surgery were recruited between January 2013 and October 2020 in the First Affiliated Hospital of Southern University of Science and Technology. The patients were divided into a hybrid group (N = 33) and a TLIF group (N = 35) by surgery. After surgery, follow-up was conducted for 12 months. Between the two groups, the following parameters were compared: general conditions, clinical symptom scores, imaging parameters, and early complications. Results: A statistically significant difference in the duration of surgery was noted between the two groups. After 12 months of follow-up, the range of motion disappeared in the TLIF group, while 63.53% was preserved in the hybrid group with statistically significant differences. A statistically significant difference was identified in the Oswestry Disability Index one week after surgery. Nonetheless, no statistically significant differences were observed at the 12-month post-surgical follow-up. Pfirrmann grade showed a 3.03% upper adjacent segment degeneration rate in the hybrid group (1/33) at 12-month follow-up and 2.86% (1/35) in the TLIF group. Notably, no early complications (screw loosening and wound infection) were identified in the two groups. Conclusion: The Dynesys hybrid surgery combined the advantages of two systems of dynamic stabilization and rigid fusion. Besides, hybrid surgery is potentially a novel approach for the treatment of multi-segmental lumbar spinal stenosis.

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