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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 310: 123911, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38277786

RESUMO

The present study discusses the fabrication of a bimetallic material consisting of silver nanorods and gold nanospheres (designated Ag@Au), and its surface modification with 4-nitrothiophenol (PNTP) after deposition on an indium tin oxide (ITO) glass sheet, followed by laser irradiation at various wavelengths. The results indicate that the reduction of PNTP is more complete under irradiation at 532 nm due to the surface plasmon resonance (SPR) effects of the gold and silver nanomaterials. Moreover, the surface enhanced Raman scattering (SERS) of the PNTP adsorbed on the Ag@Au/ITO is found to be significantly stronger than that of PNTP adsorbed on Ag@Au alone, due to charge transfer (CT) at the interface. In addition, the SERS enhancement effect of the PNTP molecules on the Ag@Au/ITO substrate is optimal under 532 nm laser irradiation due to the hot electron-induced CT generated by the SPR effect. Thus, the system constructed herein combines the effects of SPR and CT, thereby assisting in a further understanding of the enhancement mechanism of SERS and, hence, the further development SERS research in metal-semiconductor-molecular systems.

2.
Int J Cardiovasc Imaging ; 40(1): 27-34, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37843758

RESUMO

This study was designed to retrospectively analyze the relationship between the levels of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) and the development of left ventricular diastolic dysfunction (LVDD) in septic patients with diabetes mellitus. Furthermore, the predictive value of cTnT and cTnI in the LVDD development in those patients was investigated. The clinical information of 159 septic patients with diabetes mellitus treated in the intensive care unit of Affiliated Hospital of Chengde Medical University from June 2016 to January 2023 were retrospectively analyzed. These patients were separated into LVDD group (LVFP > 15 mmHg) and non-LVDD group (LVFP ≤ 15 mmHg) based on left ventricular filling pressure (LVFP). The differences in clinical data, echocardiographic parameters, as well as cTnT and cTnI levels between the LVDD and non-LVDD groups were compared. The relationship between the cTnT and cTnI levels and the echocardiographic parameters was studied using Pearson correlation analysis. Logistic regression analysis was conducted to explore the factors that influenced the LVDD development in septic patients with diabetes. Receiver operator characteristic (ROC) curves were created to evaluate the predictive value of cTnT and cTnI levels for the LVDD development in septic patients with diabetes. Totally 159 septic patients with diabetes were included in this study, with 97 patients in the LVDD group and 62 in the non-LVDD group. Compared with the non-LVDD group, patients in the LVDD group had much lower left ventricular (LV) early diastolic peak inflow velocity (E), LV advanced diastolic peak inflow velocity (A), E/A, and early diastolic mitral annular velocity (Em) while significantly higher E/Em. The LVDD group showed much higher levels of cTnI and cTnT than the non-LVDD group (P < 0.05). Significant positive correlation between log10cTnI level and E/Em ratio (r = 0.425, P < 0.001) was revealed by the Pearson correlation analysis. Multivariate analysis showed that E/A, E/Em, cTnI and cTnT were independent risk factors for the LVDD development in septic patients with diabetes (P < 0.05). As for ROC curve results, the area under the curve (AUC) of cTnT to predict the development of LVDD in septic patients with diabetes was 0.849 (95% CI 0.788-0.910, P < 0.001); the AUC of cTnI was 0.742 (95% CI 0.666-0.817, P < 0.001). Both cTnT and cTnI are independent risk factors and have predictive value for the LVDD development in septic patients with diabetes mellitus.


Assuntos
Diabetes Mellitus , Sepse , Disfunção Ventricular Esquerda , Humanos , Estudos Retrospectivos , Valor Preditivo dos Testes , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Diabetes Mellitus/diagnóstico , Sepse/complicações , Sepse/diagnóstico , Troponina , Troponina T , Biomarcadores
3.
Zhongguo Gu Shang ; 36(11): 1036-40, 2023 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-38012871

RESUMO

OBJECTIVE: To construct and evaluate nomogram prediction model for periprosthetic fractures in patients undergoing total hip arthroplasty (THA). METHODS: A total of 538 patients who underwent THA from April 2013 to February 2019 were selected as the research subjects, including 318 males and 220 females, aged 40 to 60 years old with an average age of (50.79±6.37) years old. All patients with THA were divided into non-fracture group (506 patients) and fracture group (32 pathents) according to the 3-year follow-up results. Univariate and multivariate Logistic regression analyses were performed to analyze the influencing factors of postoperative periprosthetic fractures in patients with THA. A nomogram prediction model for periprosthetic fractures in patients undergoing THA was constructed, and the validity and discrimination of the prediction model were evaluated. RESULTS: The proportion of patients with osteoporosis, trauma history, and hip revision in the fracture group were higher than those in the non-fracture group(P<0.05), and the proportion of bone cement prosthesis was lower than that in the non-fracture group(P<0.05). The osteoporosis status[OR=4.177, 95%CI(1.815, 9.617), P<0.05], trauma history[OR=7.481, 95%CI(3.104, 18.031), P<0.05], and hip revision[OR=11.371, 95%CI(3.220, 40.153, P<0.05] were independent risk factors for postoperative periprosthetic fractures in patients undergoing THA, cemented prosthesis [OR=0.067, 95%CI(0.019, 0.236), P<0.05] was an independent protective factor for postoperative periprosthetic fractures in patients undergoing THA(P<0.05). Hosmer-Lemeshow goodness of fit test showed that χ2=7.864, P=0.325;the area under the curve (AUC) for periprosthetic fractures in patients undergoing THA was 0.892 with a sensitivity of 87.5% and a specificity of 77.7% by receiver operating characteristic(ROC) curve. CONCLUSION: The nomogram prediction model for periprosthetic fractures after THA constructed in this study has good discrimination, which is beneficial to clinical prediction of periprosthetic fractures in patients undergoing THA, and facilitates individualized fracture prevention.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Osteoporose , Fraturas Periprotéticas , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Artroplastia de Quadril/efeitos adversos , Fraturas Periprotéticas/etiologia , Fraturas Periprotéticas/cirurgia , Nomogramas , Reoperação/efeitos adversos , Fatores de Risco , Osteoporose/cirurgia , Estudos Retrospectivos
4.
Sci Rep ; 13(1): 13930, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37626224

RESUMO

The Jiaozhou Bay ecosystem, a crucial marine ecosystem in China, has been plagued by frequent harmful algal blooms as due to deteriorating water quality and eutrophication. This study analyzed the temporal and spatial changes of harmful algal blooms in Jiaozhou Bay from 2000 to 2022 using the Floating Algae Index (FAI) calculated from MODIS (2000-2022) and Sentinel-2 (2015-2022) satellite image datasets. The calculation results of the image datasets were compared. The frequency of planktonic algal outbreaks was low and constant until 2017, but has increased annually since then. Algae blooms are most common in the summer and primarily concentrated along the bay's coast, middle, and mouth, with obvious seasonal and spatial distribution characteristics. Several factors influencing algal outbreaks were identified, including sea surface temperature, wind speed, air pressure, dissolved oxygen, nitrogen and phosphorus ratios, chemical oxygen demand, and petroleum pollutants. Algal bloom outbreaks in Jiaozhou Bay are expected to remain high in 2023. The findings provide crucial information for water quality management and future algal outbreak prediction and prevention in Jiaozhou Bay.


Assuntos
Baías , Aprendizado Profundo , Ecossistema , Ferramenta de Busca , Proliferação Nociva de Algas
5.
Front Cell Dev Biol ; 11: 1167476, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469575

RESUMO

[This corrects the article DOI: 10.3389/fcell.2021.784719.].

8.
J Asian Nat Prod Res ; 25(6): 595-602, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36000727

RESUMO

A new cytotoxic alkaloid, named streptothiazolidine B (1), together with three known compounds (2-4), were isolated from Streptomyces violaceoruber. The structure of the undescribed compound was established using 1D and 2D NMR, and HRESIMS. Streptothiazolidine B was isolated and identified as an amide alkaloid with a unique thiazolidine side chain and its absolute configuration was determined by a combination of NOESY experiment and ECD analysis. Streptothiazolidine B exhibited significant cytotoxic activities against two human tumor cell lines, Li-7 and A2780, with IC50 values of 7.8, and 9.1 µM. Meanwhile, compound 4 showed obvious cytotoxic activities against four human tumor cell lines, THP-1, HT29, Li-7 and A2780, with IC50 values ranging from 3.1 to 10.2 µM.


Assuntos
Alcaloides , Antineoplásicos , Neoplasias Ovarianas , Feminino , Humanos , Linhagem Celular Tumoral , Alcaloides/farmacologia , Alcaloides/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Estrutura Molecular
9.
J Phys Chem A ; 126(23): 3669-3679, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35650674

RESUMO

This article theoretically studies the photoinduced charge transfer (CT) of rigid D-B-A molecules in two-photon absorption (TPA) adjusted by the external electric fields. Using a visualization method, the dynamic changes of light-induced CT in different channels of TPA are presented through a two-dimensional (2D) transition density matrix and a three-dimensional (3D) charge different density. Here, we prove the controllability of TPA on CT under the induction of a strong electric field. Adjusting the field direction and intensity significantly affects the position of the strong absorption peak in the TPA spectra, thereby further changing the electron-hole coherence length and the degree of dispersion. Our results can promote the recognition of the optical properties of the D-B-A system in synthetic molecules and provide an idea for increasing the proportion of excited states for CT in the molecule.

10.
Biomed Pharmacother ; 151: 113164, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35609371

RESUMO

Bone marrow-derived mesenchymal stem cells (BMSCs) tend to differentiate into adipocytes rather than osteoblasts in osteoporosis and other pathological conditions. Understanding the mechanisms underlying the adipo-osteogenic imbalance greatly contributes to the ability to induce specific MSC differentiation for clinical applications. This study aimed to explore whether DEP-domain containing mTOR-interacting protein (DEPTOR) regulated MSC fate and bone-fat switch, which was indicated to be a key player in bone homeostasis. We found that DEPTOR expression decreased during the osteogenesis of BMSCs but increased during adipogenesis and the shift of cell lineage commitment of BMSCs to adipocytes in mice with osteoporosis. DEPTOR facilitated adipogenic differentiation while preventing the osteogenic differentiation of BMSCs. Deptor ablation in BMSCs alleviated bone loss and reduced marrow fat accumulation in mice with osteoporosis. Mechanistically, DEPTOR binds transcriptional coactivator with a PDZ-binding motif (TAZ) and inhibits its transactivation properties, thereby repressing the transcriptional activity of RUNX2 and elevating gene transcription by peroxisome-proliferator-activated receptor-gamma. TAZ knockdown in BMSCs abolished the beneficial role of Deptor ablation in bone-fat balance in mice. Together, our data indicate that DEPTOR is a molecular rheostat that modulates BMSC differentiation and bone-fat balance, and may represent a potential therapeutic target for age-related bone loss.


Assuntos
Osteogênese , Osteoporose , Adipogenia/genética , Animais , Diferenciação Celular/genética , Camundongos , Osteoblastos/metabolismo , Osteogênese/genética , Osteoporose/patologia
11.
Bone Res ; 10(1): 25, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35256591

RESUMO

Senescence impairs preosteoblast expansion and differentiation into functional osteoblasts, blunts their responses to bone formation-stimulating factors and stimulates their secretion of osteoclast-activating factors. Due to these adverse effects, preosteoblast senescence is a crucial target for the treatment of age-related bone loss; however, the underlying mechanism remains unclear. We found that mTORC1 accelerated preosteoblast senescence in vitro and in a mouse model. Mechanistically, mTORC1 induced a change in the membrane potential from polarization to depolarization, thus promoting cell senescence by increasing Ca2+ influx and activating downstream NFAT/ATF3/p53 signaling. We further identified the sodium channel Scn1a as a mediator of membrane depolarization in senescent preosteoblasts. Scn1a expression was found to be positively regulated by mTORC1 upstream of C/EBPα, whereas its permeability to Na+ was found to be gated by protein kinase A (PKA)-induced phosphorylation. Prosenescent stresses increased the permeability of Scn1a to Na+ by suppressing PKA activity and induced depolarization in preosteoblasts. Together, our findings identify a novel pathway involving mTORC1, Scn1a expression and gating, plasma membrane depolarization, increased Ca2+ influx and NFAT/ATF3/p53 signaling in the regulation of preosteoblast senescence. Pharmaceutical studies of the related pathways and agents might lead to novel potential treatments for age-related bone loss.

12.
ACS Omega ; 7(11): 9743-9753, 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35350325

RESUMO

In this work, density functional theory is used to study organic molecules in a donor-acceptor (D-A) system centered on phenothiazine with strip and trigonal structures. The transition modes of the one-photon absorption (OPA) and two-photon absorption (TPA) processes of the two molecules are studied. The calculations show that the molar absorption coefficient of OPA for trigonal molecule TPPO and the cross section of TPA are both larger than those for strip molecule M1 due to the increase in the number of branches of the system. A special local excitation-enhanced charge-transfer excitation appears in strip-type molecule M1. In the charge-transfer process of trigonal D-A structure molecule TPPO, there are not only local excitation-enhanced charge-transfer excitation but also super-exchange charge transfer between the three branches that occurs due to the increase in the planarity of the system.

13.
Nat Aging ; 2(10): 906-922, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-37118283

RESUMO

Although clinical evidence has indicated an association between skin atrophy and bone loss during aging, their causal relationship and the underlying mechanisms are unknown. Here we show that premature skin aging drives bone loss in mice. We further identify that cystatin-A (Csta), a keratinocyte-enriched secreted factor, mediates the effect of skin on bone. Keratinocyte-derived Csta binds the receptor for activated C-kinase 1 in osteoblast and osteoclast progenitors, thus promoting their proliferation but inhibiting osteoclast differentiation. Csta secretion decreases with skin aging in both mice and humans, thereby causing senile osteoporosis by differentially decreasing the numbers of osteoblasts and osteoclasts. In contrast, topical application of calcipotriol stimulates Csta production in the epidermis and alleviates osteoporosis. These results reveal a mode of endocrine regulation of bone metabolism in the skin, and identify Csta as an epidermally derived hormone linking skin aging to age-related bone loss. Enhancers of skin Csta levels could serve as a potential topical drug for treatment of senile osteoporosis.


Assuntos
Osteoporose , Envelhecimento da Pele , Humanos , Camundongos , Animais , Cistatina A/metabolismo , Osteoclastos/metabolismo , Osteoblastos , Osteoporose/tratamento farmacológico
14.
Materials (Basel) ; 14(23)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34885372

RESUMO

Geometric characteristics provide an important means for characterization of the quality of direct laser deposition. Therefore, improving the accuracy of a prediction model is helpful for improving deposition efficiency and quality. The three main input variables are laser power, scanning speed, and powder-feeding rate, while the width and height of the melt track are used as outputs. By applying a multi-output support vector regression (M-SVR) model based on a radial basis function (RBF), a non-linear model for predicting the geometric features of the melt track is developed. An orthogonal experimental design is used to conduct the experiments, the results of which are chosen randomly as training and testing data sets. On the one hand, compared with single-output support vector regression (S-SVR) modeling, this method reduces the root mean square error of height prediction by 22%, with faster training speed and higher prediction accuracy. On the other hand, compared with a backpropagation (BP) neural network, the average absolute error in width is reduced by 5.5%, with smaller average absolute error and better generalization performance. Therefore, the established model can provide a reference to select direct laser deposition parameters precisely and can improve the deposition efficiency and quality.

15.
Phys Chem Chem Phys ; 23(35): 19297-19307, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524280

RESUMO

The electrical contact and graphene (Gr) doping for Gr/XPtY (X, Y = S, Se, and Te) van der Waals (vdW) heterostructures are studied by using first-principles methods. The intrinsic electronic properties of Gr and PtXY are preserved due to the weak vdW interactions. We find that the types of interfacial electrical contact and Gr doping are closely related to the interface chalcogen atoms. The n-type Ohmic contact is formed in the Gr/SPtY (Y = S, Se, and Te) systems. The n-type and p-type Schottky contacts are realized in the Gr/SePtY and Gr/TePtY systems, respectively. The physical mechanism of different contact types can be analyzed based on the charge transfer between the Gr and XPtY layers. For all the heterostructures, the contact type and Schottky barrier height can be effectively modulated by the external electric field and interlayer coupling. The Gr doping type and charge-carrier concentration are also investigated. The p-doping, p-doping, and n-doping are obtained in Gr for the Gr/SPtY, Gr/SePtY, and Gr/TePtY systems, respectively. The highest carrier concentration of the Gr layer can reach 1.69 × 1013 cm-2 for the Gr/TePtTe system. The results indicate that Gr/XPtY heterostructures are potential candidates for improving the performance of high-efficiency nano electronic devices.

16.
Front Cell Dev Biol ; 9: 784719, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35096816

RESUMO

Background: Osteosarcoma (OS) is the most prevalent bone cancer among children and adolescents, with relatively high mortality rates. RNA N6-methyladenosine (m6A) is the most common human mRNA modification with diverse functions in a variety of biological processes. Previous studies indicated that methyltransferase-like 3 (METTL3), the first methyltransferase to be identified, acted as an oncogene or tumor suppressor in multiple human cancers. However, its functions and underlying mechanisms in OS progression remain unclear; therefore, we explored these processes. Methods: We used real-time quantitative PCR (RT-qPCR) and Western blot assays to explore METTL3 expression in OS tumor tissues and five OS cell lines to assess its clinical significance. To further examine the functional role of METTL3 during OS progression, CCK-8 analyses, transwell assays, and xenograft model studies were conducted after silencing METTL3. Additionally, underlying mechanisms were also explored using RIP-seq and RIP-qPCR approaches. Results: METTL3 was upregulated in OS tumor tissues and cell lines and was associated with a worse prognosis. Moreover, METTL3 silencing suppressed OS cell proliferation, migration, and invasion. Also, in vivo METTL3 oncogenic functions were confirmed in the xenograft model. Comprehensive mechanistic analyses identified long non-coding RNA (lncRNA) DANCR as a potential target of METTL3, as indicated by reduced DANCR levels after METTL3 silencing. Also, lncRNA DANCR knockdown repressed OS cell proliferation, migration, and invasion. Furthermore, both METTL3 and lncRNA DANCR silencing significantly suppressed OS growth and metastasis. Finally, we hypothesized that METTL3 regulated DANCR expression via m6A modification-mediated DANCR mRNA stability. Conclusion: METTL3 contributes to OS progression by increasing DANCR mRNA stability via m6A modification, meaning that METTL3 may be a promising therapeutic target for OS treatment.

17.
RSC Adv ; 11(39): 24366-24373, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35479044

RESUMO

Tuning the interlayer twist angle provides a new degree of freedom to exploit the potentially excellent properties of two dimensional layered materials. Here we investigate the structural and electronic properties of twisted bilayer SiC under a series of twist angles using first principle calculations. The interplay of interlayer van der Waals interactions and intralayer strain induces dramatic in-plane and out-of-plane displacements. The expansion or contraction of specific stacking domains can be interpreted as the result of the energy minimization rule. By means of order parameter analysis, the triangular or hexagonal strain soliton networks are found to separate adjacent stacking domains. The unique overlapped zigzag atom lines in strain solitons provide a unique characteristic for experimental imaging. The top valence band and bottom conduction band evolve into flat bands with the smallest band width of 4 meV, indicating a potential Mott-insulator phase. The moiré-potential-modulated localization pattern of states in the flat band, which is dependent sensitively on the structure relaxation, controls the flat band width. The moiré-pattern-induced structural and electronic properties of twisted bilayer SiC are promising for application in nanoscale electronic and optical devices.

18.
Int J Immunopathol Pharmacol ; 34: 2058738420950583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33206570

RESUMO

Septic shock (SS) leads to a high mortality rate for sepsis patients. Norepinephrine (NE) is a preferred vasoactive agent in SS treatment. This study aimed to assess the effects of NE at different administration time and NE combined with SP treatment on the cardiac function and prognosis of SS.SS patients received NE treatment at different administration time and NE combined with SP treatment were enrolled in this study. The serum levels of cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP), ejection fraction (EF), and pressure-adjusted heart rate (PAR) value were analyzed to evaluate cardiac function. The 28-day survival information was collected and assessed using the Kaplan-Meier method and log-rank test.The cardiac function of SS patients was improved significantly by NE treatment, especially in the patients received NE at 2 h after fluid infusion, which evidenced by the increased BNP and cTnI levels and EF% and the decreased RAP. In the NE-2 h group, SS patients had a better 28-day survival rate compared with those patients in NE-1 h and -3 h groups. Furthermore, the significantly improved cardiac function and survival outcomes were found in patients received NE combined SP treatment.Taken together, this study results show that NE administration at 2 h after fluid infusion may be the optimal time point for the treatment of SS and NE combined with SP treatment can improve early cardiac dysfunction and 28-day survival outcomes in patients with SS.


Assuntos
Cardiotônicos/uso terapêutico , Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Norepinefrina/uso terapêutico , Fosfocreatina/uso terapêutico , Choque Séptico/tratamento farmacológico , Adulto , Idoso , Pressão Arterial/efeitos dos fármacos , Biomarcadores/sangue , Cardiotônicos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Hidratação , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Norepinefrina/efeitos adversos , Fosfocreatina/efeitos adversos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Choque Séptico/diagnóstico , Choque Séptico/mortalidade , Choque Séptico/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Troponina I/sangue
19.
J Phys Condens Matter ; 33(4)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-32987372

RESUMO

InSe monolayer, belonging to group III-VI chalcogenide family, has shown promising performance in the realm of spintronic. Nevertheless, the out-of-plane mirror symmetry in InSe monolayer constrains the electrons' degrees of freedom, and this will confine its spin-related applications. Herein, we construct Sb/InSe van der Waals heterostructure to extend the electronic and spintronic properties of InSe. The density functional theory is utilized to verify the tunable electronic properties and Rashba spin splitting (RSS) of Sb/InSe heterostructure. According to the obtained results, the Sb/InSe heterostructure can be considered as a direct band gap semiconductor with typical type-II band alignment, where the electrons and holes are localized in the InSe and Sb layers, respectively. The RSS is recognized at conduction band minimum around Γ point in Sb/InSe, which is induced by the spontaneous internal electric field with electric dipole moment of 0.016 e Å from Sb to InSe. The vertical strain, in-plane strain, and external electric field are employed to modulate the strength of RSS. The Rashba coefficient and dipole moment exhibit the similar variation tendency, suggesting the strength of RSS depends on the magnitude of dipole moment. The controllable RSS makes Sb/InSe heterostructure become an appropriate candidate material for spintronic devices.

20.
Clin Interv Aging ; 15: 1201-1212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764906

RESUMO

INTRODUCTION: Estrogen deficiency leads to bone loss in postmenopausal osteoporosis, because bone formation, albeit enhanced, fails to keep pace with the stimulated osteoclastic bone resorption. The mechanism driving this uncoupling is central to the pathogenesis of postmenopausal osteoporosis, which, however, remains poorly understood. We previously found that Cxcl9 secreted by osteoblasts inhibited osteogenesis in bone, while the roles of Cxcl9 on osteoclastic bone resorption and osteoporosis are unclear. MATERIALS AND METHODS: Postmenopausal osteoporosis mouse model was established by bilateral surgical ovariectomy (OVX). In situ hybridization was performed to detect Cxcl9 mRNA expression in bone. ELISA assay was conducted to assess Cxcl9 concentrations in bone and serum. Cxcl9 activity was blocked by its neutralizing antibody. Micro-CT was performed to determine the effects of Cxcl9 neutralization on bone structure. Cell Migration and adhesion assay were conducted to evaluate the effects of Cxcl9 on osteoclast activity. TRAP staining and Western blot were performed to assess osteoclast differentiation. CXCR3 antagonist NBI-74,330 or ERK antagonist SCH772984 was administered to osteoclast to study the effects of Cxcl9 on CXCR3/ERK signaling. RESULTS: Cxcl9 was expressed and secreted increasingly in OVX mice bone. Neutralizing Cxcl9 in bone marrow prevented bone loss in the mice by facilitating bone formation as well as inhibiting bone resorption. In vitro, Cxcl9 secreted from osteoblasts facilitated osteoclast precursors adhesion, migration and their differentiation into mature osteoclasts. The positive role of osteoblastic Cxcl9 on osteoclasts was eliminated by blocking CXCR3/ERK signaling in osteoclasts. Estrogen negatively regulated Cxcl9 expression and secretion in osteoblasts, explaining the increased Cxcl9 concentration in OVX mice bone. CONCLUSION: Our study illustrates the roles of Cxcl9 in inhibiting bone formation and stimulating bone resorption in osteoporotic bone, therefore providing a possible therapeutic target to the treatment of postmenopausal osteoporosis.


Assuntos
Quimiocina CXCL9/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/fisiologia , Osteoporose Pós-Menopausa/metabolismo , Animais , Reabsorção Óssea , Estrogênios/metabolismo , Feminino , Humanos , Camundongos , Transdução de Sinais , Microtomografia por Raio-X
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