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1.
J Chem Inf Model ; 64(15): 5931-5943, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39042485

RESUMO

Vast published dielectric ceramics literature is a natural database for big-data analysis, discovering structure-property relationships, and property prediction. We constructed a data-mining pipeline based on natural language processing (NLP) to extract property information from about 12,900 published dielectric ceramics articles and normalized more than 20 properties. The micro-F1 scores for sentence classification, named entities recognition, relation extraction (related), and relation extraction (same), are 91.6, 82.4, 91.4, and 88.3%, respectively. We demonstrated the distribution of some essential properties according to the publication years to reveal the tendency. In order to test the reliability of the data extraction, we trained an XGBoost model to predict the dielectric constant and used the SHAP module to interpret the contribution of each feature in order to identify some of the factors that determine the dielectric properties. The result shows that including Q × f in the model can increase the dielectric constant prediction accuracy. Our work can give some hints to experimentalists on their way to improve the performances of cutting-edge materials.


Assuntos
Cerâmica , Mineração de Dados , Mineração de Dados/métodos , Cerâmica/química , Processamento de Linguagem Natural , Bases de Dados Factuais
2.
Opt Express ; 31(26): 43550-43559, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38178448

RESUMO

We demonstrate a laser-diode-pumped multipass Nd:glass laser amplifier with a range of advanced characteristics. The amplifier exhibits high extraction efficiency, enables arbitrary shaping of spatial beam intensity, and effectively suppresses frequency modulation to amplitude modulation conversion. Our approach achieves excellent beam quality via thermal lensing and thermal depolarization compensation. When a 1.82 mJ/5 ns laser pulse was injected into the amplifier, the output energy reached up to 3.3 J with a repetition rate of 1 Hz at a central wavelength of 1053.3 nm. The near-field modulation of the amplified output beam was below 1.2, and the far-field focusing ability of the beam was 90% at 2.9 times the diffraction limit. This laser amplifier system holds potential for integration as a preamplifier within the SG-II upgrade high power laser facility.

3.
Lupus ; 32(12): 1381-1393, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37751892

RESUMO

BACKGROUND: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), and its pathogenesis is not fully understood. Previously, we showed that fractalkine (FKN) expression was positively correlated with the severity of LN. Here, we aimed to study the role of the Hippo signaling pathway (HSP) and its interaction with FKN in LN in an attempt to provide novel strategies for LN treatment. METHODS: In this study, lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-stimulated THP-1 cells were co-cultured with FKN up-regulated or down-regulated kidney epithelial cells Hkb20. FKN-knockout (KO-FKN) mice were used to construct LN model. Flow cytometric analysis, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), pathological staining, Western blot, and immunofluorescence (IF) staining were employed to investigate the role of FKN and its interaction with the Hippo signaling pathway (HSP) in LN. RESULTS: Up-regulation of FKN in kidney epithelial cells was associated with increased macrophage activation. FKN overexpression in kidney epithelial cells suppressed apoptosis, inflammation levels, and M1 polarization of THP-1 cells and inhibited the HSP. Oppositely, FKN knockdown in kidney epithelial cells increased apoptosis, inflammation, and M1 polarization and activated the HSP. HSP inhibitor reversed the effect of FKN knockdown on THP-1 cells. In LN mice, FKN knockout and YAP inhibitor decreased the levels of renal function markers, alleviated kidney injury induced by LN, and inhibited macrophage activation in LN mice. CONCLUSIONS: FKN down-regulation reduced the activation of macrophages in renal tissue and alleviated kidney damage by activating HSP. The regulatory effect of FKN on HSP should be confirmed in patients with LN, and the mechanism of FKN in LN should be further explored.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Animais , Humanos , Camundongos , Quimiocina CX3CL1/metabolismo , Células Epiteliais/metabolismo , Via de Sinalização Hippo , Inflamação/metabolismo , Rim/patologia , Lúpus Eritematoso Sistêmico/metabolismo , Nefrite Lúpica/patologia , Ativação de Macrófagos
4.
BMC Musculoskelet Disord ; 24(1): 953, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066443

RESUMO

BACKGROUND: Metabolomics is a tool to study the pathogenesis of diseases and their associated metabolites, but there are still insufficient metabolomic studies on severe knee osteoarthritis.To investigate the differences in serum metabolites between healthy populations and knee osteoarthritis (KOA) patients in Southern China using widely targeted metabolomics, and to explore biomarkers and their metabolic pathways that could be associated with the severity of KOA. METHODS: There were 10 healthy individuals in the control group and 32 patients with KOA. According to the Kellgren-Lawrence (KL) grading system, KOA was further divided into mild (n = 13, KL grade 1 and 2) and severe (n = 19, KL grade 3 and 4). Serum samples from all participants were collected and analyzed metabolomics based on ultra-performance liquid chromatography/electrospray ionization/tandem mass spectrometry. We screened for differential metabolites between patients and controls, and between mild and severe KOA. We explored the metabolic pathways involved in differential metabolism using the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: Sixty-one metabolites were differentially expressed in the sera of the patient group compared with the control group (45 upregulated and 16 downregulated). Analysis of the mild and severe KOA groups showed a total of 12 differential metabolites. Receiver operating characteristic curve analysis showed N-alpha-acetyl-L-asparagine was a good predictor of advanced osteoarthritis(OA).Differential metabolites are enriched in multiple pathways such as arachidonic acid metabolism. CONCLUSION: Widely targeted metabolomics found that upregulation of the amino acid metabolite N-α-acetyl-L-asparagine was significantly associated with severe KOA and could be a biomarker for predicting severity of KOA. Arachidonic acid metabolism may play an important role in patients with severe KOA.


Assuntos
Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/complicações , Ácido Araquidônico , Asparagina , Metabolômica , Biomarcadores
5.
Opt Express ; 29(11): 15980-15994, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34154171

RESUMO

A high-energy, high-beam-quality, high-contrast picosecond optical parametric chirped-pulse amplification (ps-OPCPA) laser system was demonstrated. The pulse from a femtosecond oscillator was stretched to 4 ps, after which it was amplified from 140 pJ to 600 µJ by an 8 ps/6 mJ pump laser in two non-collinear OPCPA stages. The total gain was >106, and the root mean square of the energy stability of the laser system was 1.6% in 10 h. The contrasts of the solid and fiber mode-locked femtosecond oscillator-seeded ps-OPCPA systems were compared, and a signal-to-noise ratio of >1011 was achieved. Using this system, the contrast of the front end in high-power picosecond petawatt laser facility was improved by ∼40 dB to >1011, beyond ∼200 ps ahead of the main pulse with an output level of 60 mJ.

6.
Appl Opt ; 59(20): 6070-6075, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32672752

RESUMO

A high-energy, high-beam-quality, and pulse-width-tunable Nd:YAG laser system, pumped by vertical cavity surface emitting laser arrays and laser diodes, is demonstrated and applied to a velocity interferometry system for any reflector (VISAR) application in a high power laser facility. A multistage multipass amplification structure is used to fully extract the amplifier energy and obtain a high-energy pulse. The temporal waveform is compensated to provide a square waveform, with a flatness less than 8% (peak-to-peak value). The peak power is greater than 100 kW with a frequency-doubling efficiency of 25% for a 50 ns pulse width. The laser operates as a single shot with 1-5 Hz repetition frequency and 0.7% rms energy stability.

7.
Opt Express ; 27(5): 7545-7559, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30876317

RESUMO

As the ultrafast laser has been developed, the measurement of ultra-speed transient and dynamic processes has gained much attention. An ultrafast oscilloscope based on the optical stretch method is promising to address this problem, but the measurement is restricted to the temporal profile. This means that the temporal phase is lost. In this work, we propose a full-field ultrafast oscilloscope using two temporal phase retrieval methods: the temporal annealing Gerchberg-Saxton (TAGS) algorithm and temporal ptychography. These could provide complete information, including temporal profile and phase, of high-rate repetitive transient pulses. The functions of an ultrafast oscilloscope with 230 GHz bandwidth and the two phase retrieval methods are verified by simulation and experimental results. This full-field ultrafast oscilloscope promises more applications in phase encoding, phase-contrast imaging, and sensing in the time domain.

8.
Cancer Cell Int ; 19: 153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171917

RESUMO

BACKGROUND: Lymphoma is one of the most common hematologic malignancy. Drug resistance is the main obstacle faced in lymphoma treatment. Cancer stem cells are considered as the source of tumor recurrence, metastasis and drug resistance. The ß-Asarone, a low-toxicity compound from the traditional medical herb Acorus calamus, has been shown to act as an anti-cancer reagent in various cancer types. However, the anti-cancer activities of ß-Asarone in lymphoma have not been shown. METHODS: Cell counting assay was used to evaluate Raji cell proliferation. CCK8 assay was used to evaluate the cell viability. Annexin-V/PI staining and flow cytometry analysis were used to evaluate apoptosis. ALDEFLUOR assay was used to evaluate the stem-like population. Luciferase reporter assay was used to examine the activation of NF-κB signaling. Western blot and polymerase chain reaction (PCR) were used to determine the expression of interested genes. RESULTS: We showed that ß-Asarone inhibited proliferation and induced apoptosis in Raji lymphoma cells in a dose-dependent manner. Additionally, ß-Asarone functioned as a sensitizer of doxorubicin and resulted in synergistic effects on inhibition of proliferation and induction of apoptosis when combined with doxorubicin treatment. Interestingly, we found that ß-Asarone also reduced the stem-like population of Raji lymphoma cells in a dose-dependent manner, and suppressed the expression of c-Myc and Bmi1. Importantly, ß-Asarone abolished doxorubicin-induced enrichment of the stem-like population. In the mechanism study, we revealed that ß-Asarone suppressed not only basal NF-κB activity but also Tumor necrosis factor α (TNF-α) induced NF-κB activity. Moreover, blocking NF-κB signaling inactivation was critical for ß-Asarone induced apoptosis and inhibition of proliferation, but not for the effect on ß-Asarone reduced stem-like population. In fact, ß-Asarone suppressed stem-like population by destabilizing Bmi1 via a proteasome-mediated mechanism. CONCLUSIONS: Our data suggested the application of ß-Asarone to lower the toxic effect of doxorubicin and increase the sensitivity of doxorubicin in clinical treatment. More importantly, our data revealed a novel role of ß-Asarone which could be used to eliminate stem-like population in lymphoma, implying that ß-Asarone might reduce relapse and drug resistance.

9.
Appl Opt ; 57(34): 9898-9906, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30645280

RESUMO

The temporal contrast levels of laser pulses in the injection laser system of the Shenguang-II facility are accurately measured and analyzed in detail. These signal-to-noise ratio levels are determined by the extinction ratios of an acousto-optic modulator, an electro-optic intensity modulator, and a combination of a Pockels cell and thin film polarizers. In addition, a drifting direct current bias voltage of an electro-optic intensity modulator and phase modulation are also demonstrated to affect the signal-to-noise ratio of the injection laser system. With a precise control of these factors, the injection laser system can output a nanosecond laser pulse with a signal-to-noise ratio of 47.37 dB. Moreover, a nanosecond laser pulse signal-to-noise ratio measuring device with a dynamic range and accuracy of 50 and 1 dB, respectively, is developed to detect the signal-to-noise ratio of a nanosecond laser pulse, which is 47.06 dB within an accuracy range of 1 dB. The signal-to-noise ratio measuring device can detect the high contrast laser pulse for the seed source unit in the high power laser facility accurately and conveniently.

10.
Appl Opt ; 56(6): 1610-1615, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28234367

RESUMO

FM-AM modulation of high-power lasers significantly affects laser performance. Therefore, precise measurement of the FM-AM modulation depth is necessary. The subsequent FM-AM modulation generated by group velocity dispersion when the laser pulse propagates through a fiber affects the measurement accuracy. In order to eliminate this effect, a waveform-acquisition module is proposed that converts a broad-spectrum pulse of 1053 nm to a narrow-spectrum pulse of 1550 nm, without affecting the waveform. In addition, a signal-processing algorithm based on the orthogonal matching pursuit method is implemented to remove the sampling noise from the waveform. In this way, the signal-to-noise ratio of the measurement can be readily improved. Both theoretical and experimental results indicate that the proposed FM-AM modulation detection system is effective and economical. It can measure the FM-AM modulation depth precisely, and therefore shows considerable promise for future applications in high-power lasers.

11.
Appl Opt ; 56(8): 2294-2300, 2017 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-28375275

RESUMO

In order to characterize ultrashort pulses in real time at 1 µm wavelength, a temporal imaging structure based on the four-wave mixing effect in highly nonlinear fibers is implemented and analyzed both theoretically and experimentally. It is found that both time-frequency transfer and the temporal magnification process can be realized approximately in one structure. The pulse widths of the signal laser measured by the time-frequency transfer and the temporal magnification process are 3.2 ps and 3.1 ps, respectively, which are nearly the same and are in agreement with the result of the autocorrelator. The temporal magnification factor is 33, and the temporal resolution is 380 fs. The method based on the temporal magnification process is inherently real time and single shot, which makes it suitable for applications in the measurement of high-power ultrashort pulses. The four-wave mixing time lens promises future applications in the characterization of the single-shot high-power short laser.

12.
Appl Opt ; 55(29): 8352-8358, 2016 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-27828086

RESUMO

FM-to-AM modulation is an important effect in the front end of high-power lasers that influences the temporal profile. Various methods have been implemented in standard-fiber and polarization-maintaining (PM)-fiber front ends to suppress the FM-to-AM modulation. To analyze the modulation in the front end, a theoretical model is established and detailed simulations carried out that show that the polarizing (PZ) fiber, whose fast axis has a large loss, can successfully suppress the modulation. Moreover, the stability of the FM-to-AM modulation can be improved, which is important for the front end to obtain a stable output. To verify the model, a PZ fiber front end is constructed experimentally. The FM-to-AM modulation, without any compensation, is less than 4%, whereas that of the PM fiber front end with the same structure is nearly 20%. The stability of the FM-to-AM modulation depth is analyzed experimentally and the peak-to-peak and standard deviation (SD) are 2% and 0.38%, respectively, over 3 h. The experimental results agree with the simulation results and both prove that the PZ fiber front end can successfully suppress the FM-to-AM conversion. The PZ fiber front end is a promising alternative for improving the performance of the front end in high-power laser facilities.

13.
Opt Lett ; 40(18): 4214-7, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26371899

RESUMO

We report a high-energy and high-gain fiber regenerative amplifier for narrow-bandwidth nanosecond laser pulses that uses a Yb-doped photonic crystal fiber. The input pulse energy is 270 pJ for a 3.5 ns laser pulse with 0.3 nm (FWHM) bandwidth. At a pump laser power of 8.6 W at 974 nm, pulse energies up to 746 µJ with 1.2% (rms) energy stability are generated. To the best of our knowledge, this is the highest energy obtained in a fiber-based regenerative amplifier. A high-energy, nearly diffraction-limited, single-mode beam with a high gain of 64 dB shows promise for future application in the front ends of high-power laser facilities.

14.
J Hazard Mater ; 468: 133724, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38382336

RESUMO

In the present study, we pyrolyzed a waste tire at various temperatures under an N2 atmosphere and a water environment in an autoclave reactor to investigate the effect of water on tire degradation. The analysis involved a comparison of product distribution, char properties, oil composition, and the behavior of heteroatom elements (especially oxygen, nitrogen, and sulfur) under different atmospheres. Elemental analysis, functional-group identification, and chemical state analysis of sulfur were performed for chars. In addition, the chemical composition, elemental composition, and molecular weight of the produced oils were evaluated. The heavy fraction of oils, not detectable by gas chromatography-mass spectrometry (GC-MS), was analyzed through Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The findings revealed that high temperatures promoted oil cracking, resulting in the formation of light oils in both pyrolysis and hydrolysis processes. Compared to pyrolysis, hydrolysis generated a higher yield of low molecular-weight oil. Elevated hydrolysis temperatures promoted aromatization, yielding an oil with a low H/C ratio and a high double bond equivalent number. Consequently, the concentration of aromatics in the light fraction of oils generated from the hydrolysis process exceeded that in oils from the pyrolysis process. Temperature exhibited a limited impact on oil composition during the pyrolysis process. Hydrolysis promoted the release of heteroatom-containing compounds at low temperatures. During pyrolysis, nitrogen was gradually released from the solid phase, whereas nitrogen-containing compounds were released early during hydrolysis, with gas-phase nitrogen accounting for more than 50 wt% at 320 °C. A maximum D-limonene yield of 45.58% was obtained at 360 °C within 0 min of hydrolysis, with the potential conversion of D-limonene into aromatics at higher hydrolysis temperatures. These results contribute to the understanding of tire valorization via hydrolysis.

15.
Int Immunopharmacol ; 127: 111322, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38064814

RESUMO

AIM OF THE STUDY: This study aims to reveal the role of Tanshinone I (TI) in inhibiting osteoclast activity and bone loss in vitro and in vivo, as well as elucidate its underlying molecular mechanism. MATERIALS AND METHODS: A mouse model of estrogen deficiency was used to assess the inhibitory effect of TI on osteoclast activity and subsequent bone loss. To validate the impact of TI on osteoclast formation, TRAcP staining and pseudopodia belt staining were conducted. The expressions of osteoclast-specific genes and proteins were evaluated using RT-PCR and Western Blot analyses. Additionally, immunofluorescence staining was employed to examine the effect of TI on p65 nuclear translocation and the expression level of reactive oxygen species (ROS). RESULTS: TI demonstrated significant efficacy in alleviating bone mass loss and suppressing osteoclast activity and function in ovariectomized mice. This outcome was predominantly ascribed to a decrease in ROS levels, thereby impeding the NF-κB signaling pathway and the translocation of p65 to the nucleus. Additionally, TI hindered the RANKL-induced phosphorylation of the MAPK signaling pathway. Moreover, TI played a role in the reduction of osteoclast-specific genes and proteins. CONCLUSIONS: To summarize, this study sheds light on TI's capacity to modulate various signaling pathways triggered by RANKL, effectively impeding osteoclast formation and mitigating bone loss resulting from estrogen deficiency. Consequently, TI emerges as a promising therapeutic option for estrogen-deficiency bone loss.


Assuntos
Abietanos , Doenças Ósseas Metabólicas , Reabsorção Óssea , Camundongos , Animais , NF-kappa B/metabolismo , Osteogênese , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Osteoclastos , Estrogênios/farmacologia , Estrogênios/uso terapêutico , Estrogênios/metabolismo , Ligante RANK/metabolismo , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Diferenciação Celular
16.
Foods ; 13(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38397562

RESUMO

Colitis is a chronic disease associated with alterations in the composition of gut microbiota. Schisandra chinensis bee pollen extract (SCPE) has been proved to be rich in phenolic compounds and effective in modulating gut microbiota, but its effect on colitis and the underlying mechanism remains unclear. This study investigates the relationship between colitis amelioration and the gut microbiota regulation of SCPE via fecal microbial transplantation (FMT). The results showed that administration of 20.4 g/kg BW of SCPE could primely ameliorate colitis induced by dextran sulfate sodium (DSS) in mice, showing as more integration of colon tissue structure and the colonic epithelial barrier, as well as lower oxidative stress and inflammation levels compared with colitis mice. Moreover, SCPE supplement restored the balance of T regulatory (Treg) cells and T helper 17 (Th17) cells. Gut microbiota analysis showed SCPE treatment could reshape the gut microbiota balance and improve the abundance of gut microbiota, especially the beneficial bacteria (Akkermansia and Lactobacillus) related to the production of short-chain fatty acids and the regulation of immunity. Most importantly, the protection of 20.4 g/kg BW of SCPE on colitis can be perfectly transmitted by fecal microbiota. Therefore, the gut microbiota-SCFAS-Treg/Th17 axis can be the main mechanism for SCPE to ameliorate colitis. This study suggests that SCPE can be a new promising functional food for prevention and treatment of colitis by reshaping gut microbiota and regulating gut immunity.

17.
iScience ; 27(6): 110111, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38957790

RESUMO

Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis (KOA). We conducted 16S rDNA sequencing and untargeted metabolomics on fecal and serum samples from 20 healthy volunteers, 80 KOA patients in Guangdong, and 100 in Inner Mongolia, respectively. Through bioinformatics analysis, we identified 3 genera and 5 serum metabolites associated with KOA osteophyte formation. Blautia abundance negatively correlated with meat, cheese, and bean consumption. The 5 serum metabolites negatively correlated with dairy, beef, cheese, sugar, and salt intake, yet positively with age and oil consumption. Higher Blautia levels in the gut may contribute to KOA osteophyte formation, with serum metabolites LTB4 and PGD2 potentially serving as biomarkers. KOA patients in Inner Mongolia exhibited lower Blautia levels and reduced expression of 5 serum metabolites, possibly due to cheese consumption habits, resulting in less osteophyte formation.

18.
Science ; 383(6681): 388-394, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38271502

RESUMO

Identifying a suitable water-soluble sacrificial layer is crucial to fabricating large-scale freestanding oxide membranes, which offer attractive functionalities and integrations with advanced semiconductor technologies. Here, we introduce a water-soluble sacrificial layer, "super-tetragonal" Sr4Al2O7 (SAOT). The low-symmetric crystal structure enables a superior capability to sustain epitaxial strain, allowing for broad tunability in lattice constants. The resultant structural coherency and defect-free interface in perovskite ABO3/SAOT heterostructures effectively restrain crack formation during the water release of freestanding oxide membranes. For a variety of nonferroelectric oxide membranes, the crack-free areas can span up to a millimeter in scale. This compelling feature, combined with the inherent high water solubility, makes SAOT a versatile and feasible sacrificial layer for producing high-quality freestanding oxide membranes, thereby boosting their potential for innovative device applications.

19.
Front Immunol ; 14: 1217466, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37359559

RESUMO

Osteoarthritis is non-inflammatory degenerative joint arthritis, which exacerbates disability in elder persons. The molecular mechanisms of osteoarthritis are elusive. Ubiquitination, one type of post-translational modifications, has been demonstrated to accelerate or ameliorate the development and progression of osteoarthritis via targeting specific proteins for ubiquitination and determining protein stability and localization. Ubiquitination process can be reversed by a class of deubiquitinases via deubiquitination. In this review, we summarize the current knowledge regarding the multifaceted role of E3 ubiquitin ligases in the pathogenesis of osteoarthritis. We also describe the molecular insight of deubiquitinases into osteoarthritis processes. Moreover, we highlight the multiple compounds that target E3 ubiquitin ligases or deubiquitinases to influence osteoarthritis progression. We discuss the challenge and future perspectives via modulation of E3 ubiquitin ligases and deubiquitinases expression for enhancement of the therapeutic efficacy in osteoarthritis patients. We conclude that modulating ubiquitination and deubiquitination could alleviate the osteoarthritis pathogenesis to achieve the better treatment outcomes in osteoarthritis patients.


Assuntos
Osteoartrite , Ubiquitina-Proteína Ligases , Humanos , Idoso , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo , Enzimas Desubiquitinantes/metabolismo , Ubiquitinas/metabolismo
20.
Chin Med ; 18(1): 42, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37076903

RESUMO

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by loss of joint function, which seriously reduces the quality of life of the elderly and imposes a heavy socioeconomic burden worldwide. Monotropein (MON), the main active ingredient of Morinda officinalis F.C. How, has exhibited therapeutic effects in different disease models. However, its potential effects on chondrocytes in an arthritic model remain unclear. This study aimed to evaluate the effects of MON in chondrocytes and a mouse model of OA, and explore the potential mechanisms. MATERIALS AND METHODS: Murine primary chondrocytes were pretreated with 10 ng/ml interleukin (IL)-1ß for 24 h to establish an in vitro model of OA, and then treated with different concentrations of MON (0, 25, 50 and 100 µM) for 24 h. The proliferation of the chondrocytes was assayed using ethynyl-deoxyuridine (EdU) staining. Immunofluorescence staining, western blotting and TUNEL staining were performed to assess the effects of MON on cartilage matrix degradation, apoptosis and pyroptosis. The mouse model of OA was constructed by surgical destabilization of the medial meniscus (DMM), and the animals were randomly divided into the sham-operated, OA and OA + MON groups. Following OA induction, the mice were given intraarticular injection of 100 µM MON or equal volume of normal saline twice a week for 8 weeks. The effects of MON on cartilage matrix degradation, apoptosis and pyroptosis were assessed as indicated. RESULTS: MON significantly accelerated the proliferation of chondrocytes, and inhibited cartilage matrix degradation, apoptosis and pyroptosis in the IL-1ß-stimulated cells by blocking the nuclear factor-kappa B (NF-κB) signaling pathway. In the mouse model as well, MON treatment alleviated OA progression and promoted cartilage repair by inhibiting cartilage matrix degradation, and chondrocyte apoptosis and pyroptosis through the inactivation of the NF-κB signaling pathway. Furthermore, the MON-treated arthritic mice exhibited better articular tissue morphology and lower OARSI scores. CONCLUSIONS: MON alleviated OA progression by inhibiting cartilage matrix degradation, and the apoptosis and pyroptosis of chondrocytes via NF-κB pathway inactivation, and is a promising alternative for the treatment of OA.

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