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1.
Bioact Mater ; 8: 309-324, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34541403

RESUMO

Polyetheretherketone (PEEK) has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance. However, its biological inertness, poor osteoinduction, and weak antibacterial activity make the clinical applications in a dilemma. Inspired by the mussel adhesion mechanism, here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins (Mfps)-mimic peptide with clickable azido terminal. The peptide enables mussel-like adhesion on PEEK biomaterial surfaces, leaving azido groups for the further steps of biofunctionalizations. In this study, antimicrobial peptide (AMP) and osteogenic growth peptide (OGP) were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair. Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios, an optimal PEEK surface was finally obtained in this research, which could long-term inhibit bacterial growth, stabilize bone homeostasis and facilitate interfacial bone regeneration. In a word, this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants, in particular, achieving rational integration of multiple biofunctions to match clinical requirements.

2.
J Colloid Interface Sci ; 606(Pt 2): 1866-1873, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34507177

RESUMO

A series of Sm-Mn perovskite@mullite composites with different amounts of acid sites were successfully synthesized by regulating the level of in situ etched-surface modification. X-ray diffraction (XRD) test showed that the crystal structure of catalyst gradually changed from perovskite to perovskite@mullite composites and mullite. The characterization of temperature programmed desorption with ammonia (NH3-TPD) confirmed the acid sites on the surface of catalyst can be deployed by the in-situ modification. The temperature-programmed reduction with hydrogen (H2-TPR), and N2 adsorption-desorption showed that the surface modification also increased the reducibility, surface area, and mesoporosity of catalyst. The catalytic activities were compared by a long-term catalytic oxidation of chlorobenzene evaluation for 20 h of uninterrupted reaction at a relatively low temperature of 300 °C, and the Sm-Mn perovskite@mullite composite (SMPM-1.2) possessed the best catalytic stability. The X-ray photoelectron spectroscopy (XPS) measurement determined that the high ratios of lattice oxygen and tetravalent manganese did not improve the stability of catalyst in the catalytic oxidation of chlorobenzene, but the activities trends of samples were consistent with the change of surface (Mn4++Mn3+)/Mn2+ ratios. Meanwhile, the catalytic experiments for benzene, toluene, o-xylene and acetone showed that the as-prepared catalyst was also suitable for the efficient removal of the different types of VOCs. This work supplied a method for the further development of high activity catalysts for the removal of VOCs.

3.
Dev Comp Immunol ; 127: 104300, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34673140

RESUMO

Toll-like receptors (TLRs) play a critical role in the innate immune response of fish. In this study, we isolated the cDNA sequence of Nile tilapia TLR1 (OnTLR1). The deduced OnTLR1 protein contains a signal peptide, 7 leucine-rich repeats (LRRs), a C-terminal LRR (LRR-CT), a transmembrane region and a highly conserved TIR domain. In healthy Nile tilapia, the OnTLR1 transcript was broadly expressed in all examined tissues, with the highest expression levels in the spleen. After infection with Streptococcus agalactiae, the OnTLR1 transcripts were upregulated in the gill and kidney. After stimulation with polyinosinic-polycytidylic acid (poly(I:C)), the expression levels of OnTLR1 were significantly downregulated in the intestine, whereas OnTLR1 transcripts were significantly upregulated in the kidney. After challenge with lipopolysaccharide (LPS), the expression levels of OnTLR1 were significantly upregulated in the spleen and kidney. The subcellular localization showed that OnTLR1 was expressed in the cytoplasm. TLR1 significantly increased MyD88-dependent NF-κB activity. However, the results of a pull-down assay showed that OnTLR1 did not interact with MyD88 or TIRAP. Binding assays revealed the specificity of OnTLR1 for pathogen-associated molecular patterns (PAMPs) and bacteria that included S. agalactiae, Aeromonas hydrophila and poly(I:C) and LPS. Taken together, these findings suggest that OnTLR1, as a pattern recognition receptor (PRR), might play an important role in the immune response to pathogen invasion.

4.
J Agric Food Chem ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851104

RESUMO

N-Acetylneuraminic acid (NeuAc) is widely used as a supplement to promote brain health and enhance immunity. However, the low efficiency of de novo NeuAc synthesis limits its cost-efficient bioproduction. Herein, a synthetic multiplexed pathway engineering (SMPE) strategy is proposed to improve NeuAc synthesis. First, we compare the key enzyme sources and optimize the expression levels of three NeuAc synthesis pathways in Bacillus subtilis; the AGE, NeuC, and NanE pathways, for which NeuAc production reached 3.94, 5.67, and 0.19 g/L, respectively. Next, these synthesis pathways were combined and modularly optimized via the SMPE strategy, with production reaching 7.87 g/L. Finally, fed-batch fermentation in a 5 L fermenter reached 30.10 g/L NeuAc production, the highest reported production using glucose as the sole carbon source. Using a generally regarded as safe strain as a production host, the developed NeuAc-producing approach should be favorable for efficient bioproduction, without the need for plasmids, antibiotics, or chemical inducers.

5.
Crit Rev Food Sci Nutr ; : 1-24, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34852703

RESUMO

Excessive use of pesticides can cause contamination of the environment and agricultural products that are directly threatening human life and health. Therefore, in the process of food safety supervision, it is crucial to conduct sensitive and rapid detection of pesticide residues. The recognition element is the vital component of sensors and methods for fast testing pesticide residues in food. Improper recognition elements may lead to defects of testing methods, such as poor stability, low sensitivity, high economic costs, and waste of time. We can use the molecular biological technique to address these challenges as a good strategy for recognition element production and modification. Herein, we review the molecular biological methods of five specific recognition elements, including aptamers, genetic engineering antibodies, DNAzymes, genetically engineered enzymes, and whole-cell-based biosensors. In addition, the application of these identification elements combined with biosensor and immunoassay methods in actual detection was also discussed. The purpose of this review was to provide a valuable reference for further development of rapid detection methods for pesticide residues.

6.
Inorg Chem ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855394

RESUMO

By systematic ligand tuning for control of the secondary building units, the use of tridentate carboxylic acid to construct the rod scandium metal-organic framework NTUniv-55 (NTUniv = Nantong University) with high chemical stability and interesting selective gas adsorption was reported.

7.
ACS Appl Mater Interfaces ; 13(45): 53659-53670, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34726383

RESUMO

Advanced antibacterial methods are urgently needed to deal with possible infectious diseases. As promising alternatives to antibiotics, enzyme-mimic nanocatalysts face bottlenecks of low activities and indistinct catalytic mechanisms, which seriously restrict their development for anti-infection treatment. Herein, metastable copper sulfide (Cu2-xS) nanozymes with diversiform sizes and compositions were selected to adjust the electronic structure for enhancing enzyme-mimic activities. The as-synthesized large and thin nanoplates (L/TN nanoplates), with the stoichiometric ratio of Cu1.25S, were proven to possess the optimal peroxidase (POD)-mimic activity. Using quantum mechanics, it was theoretically revealed that the sulfur vacancies could alter the electronic structure of copper active sites and thus reduce the reaction energy barrier of H2O2 to·OH to promote the POD-mimic performance. Moreover, through enhanced enzyme-mimic activities, L/TN nanoplates achieved efficient depletion of glutathione and ascorbic acid for improving antibacterial performances. Further, synergizing with the NIR irradiation, the satisfactory destruction capability for bacteria and biofilm was achieved for L/TN nanoplates under an inflammatory level of hydrogen peroxide (50 µM). Altogether, this work provides a deeper understanding of geometrical and electronic properties-dependent antibacterial performance, and paves the way toward precise compositions and structures engineering of nanozymes.

8.
Acta Biomater ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34757232

RESUMO

Pancreatic cancer (PC) is the most lethal malignancy due to its high metastatic ability and poor drug permeability. Here, a synergized interventional photothermal-immunotherapy strategy was developed with imaging guidance and temperature monitoring by magnetic resonance imaging (MRI) technique, for the local treatment of metastatic PC. A tumor microenvironment (TME)-responsive nanoplatform was fabricated via coating of DSPE-PEG and indocyanine green (ICG) onto imiquimod (IMQ) loaded amorphous iron oxide nanoparticles (IONs). This unique nanoplatform, IMQ@IONs/ICG, served as a contrast agent for MRI, a drug delivery vehicle for IMQ and ICG, and a catalyst for TME modulation. The biodegradable IMQ@IONs/ICG was also non-toxic, and improved the penetration of the loaded drugs in PC to maximize thermal ablation of the tumor and minimize damage to the surrounding healthy tissue. For the treatment of aggressive, metastatic Panc02-H7 pancreatic tumors in mice, ION-assisted MRI was employed to guide the administration of interventional photothermal therapy (IPTT) and monitor the temperature distribution in target tumor and surrounding tissue during treatment. The local IPTT treatment induced in situ immunogenic cell death (ICD), and, in combination with released IMQ, triggered a strong antitumor immunity, leading to decreased metastases and increased CD8+ in spleen and tumors. With precise local treatment and monitoring, treated primary tumors were completely eradicated, mesentery metastases were dramatically reduced, and the survival time was significantly prolonged, without damage to normal tissue and systemic autoimmunity. Overall, this synergistic strategy represents a promising approach to treat PC with significant potential for clinical applications. STATEMENT OF SIGNIFICANCE: Pancreatic cancer (PC) is one of the most lethal malignancies because it is non-permeable to drugs and highly metastatic. In this study, we designed a tumor microenvironment-responsive amorphous iron oxide nanoplatform (ION) to co-deliver photothermal agent (ICG) and toll-like-receptor-7 agonist (IMQ). This biodegradable nanoplatform IMQ@IONs/ICG improved the penetration of the loaded drugs in pancreatic tumor. With MR imaging guidance and temperature monitoring, the precise interventional photothermal therapy on mouse Panc02-H7 orthotopic tumors releases tumor antigens to initiate tumor-special immune responses, amplified by the released IMQ. Our results demonstrate that IMQ@IONs/ICG overcomes the obstacle of drug delivery to pancreatic tumors, and when combined with photothermal therapy, induces a systemic antitumor immunity to control metastatic tumors.

9.
Genet Test Mol Biomarkers ; 25(11): 727-732, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34788144

RESUMO

Purpose: Prostatic ductal adenocarcinoma (PDA) is recognized as an advanced stage cancer and is often observed in conjunction with acinar adenocarcinoma, with abundant cytoplasm arranged in a papillary pattern. When compared with acinar adenocarcinoma, it is characterized by an increased biochemical recurrence rate and unusual metastasis sites. The purpose of the present study was to further elucidate the genomic alterations associated with PDA. Methods: Whole-exome sequencing (WES) and linkage analyses were performed on genomic DNA isolated from formalin-fixed, paraffin-embedded (FFPE) samples obtained from eleven PDA tumors and paired benign tissues. The profiles of somatic mutations, indels as well as copy-number alterations were confirmed in PDA patients. The clonal evolution patterns of the eleven PDA cases were compared with the data obtained from the Cancer Genome Atlas (TCGA) for eight primary prostatic acinar adenocarcinoma patients. Results: The same somatic changes were observed in PDA as in advanced and/or metastatic acinar adenocarcinomas. For example, the mutations of a known prostate cancer driver gene CDKN1A, were the most significant events among 17% of tumors. In addition to the known amplification of chromosomes 1q, 4p, 8q, and 14q, the copy number of several large regions also increased significantly. The origin of PDA was heterogeneous: some patients (e.g. P5) were consistent with the monoclonal model, while others (e.g. P7) were polyclonal. Conclusions: PDA and acinar adenocarcinomas of prostate with high Gleason score have similar mutational profiles. The somatic mutations in PDA may be the reason for its invasive biological behavior.

10.
J Asian Nat Prod Res ; : 1-8, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34791976

RESUMO

Two new cassane-type derivatives (1-2), together with three known compounds (3-5), were isolated from the seed kernels of Caesalpinia sinensis. Their structures were elucidated on the basis of interpretation of comprehensive spectroscopic data, including HRESIMS and 1D/2D NMR spectroscopy, and the absolute configuration were established by means of ECD calculation. Compound 2, possessing a 16-degradative cassane skeleton, was rarely encountered in cassane diterpenoids isolated from the genus Caesalpinia. All compounds were evaluated for their anti-inflammatory activities against the overproduction of NO in LPS-stimulated RAW 264.7 macrophages, and compounds 1-5 could inhibit production of NO at the concentration of 50 µM.

11.
Front Plant Sci ; 12: 767667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759949

RESUMO

Multiple C2 domain and transmembrane region proteins (MCTPs) are a group of evolutionarily conserved proteins and show emerging roles in mediating protein trafficking and signaling transduction. Although, several studies showed that MCTPs play important roles during plant growth and development, their biological functions in cotton remain largely unknown. Here, we identify and characterize 33 GhMCTP genes from upland cotton (Gossypium hirsutum) and reveal the diverse expression patterns of GhMCTPs in various tissues. We also find that GhMCTP7, GhMCTP12, and GhMCTP17 are highly expressed in the main stem apex, suggesting their possible roles in shoot development. Through analyzing different cotton species, we discover plant heights are closely related to the expression levels of GhMCTP7, GhMCTP12, and GhMCTP17. Furthermore, we silence the expression of GhMCTP genes using virus-induced gene silencing (VIGS) system in cotton and find that GhMCTP7, GhMCTP12, and GhMCTP17 play an essential role in shoot meristem development. GhMCTPs interact with GhKNAT1 and GhKNAT2 and regulate meristem development through integrating multiple signal pathways. Taken together, our results demonstrate functional redundancy of GhMCTPs in cotton shoot meristem development and provide a valuable resource to further study various functions of GhMCTPs in plant growth and development.

12.
Front Cardiovasc Med ; 8: 715337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760938

RESUMO

Objective: Atherosclerosis is an arterial occlusive disease with hypercholesterolemia and hypertension as common risk factors. Advanced-stage stenotic plaque, which features inflammation and necrotic core formation, is the major reason for clinical intervention. Receptor interacting serine/threonine-protein kinase 1 (RIPK1) mediates inflammation and cell death and is expressed in atherosclerotic lesions. The role of RIPK1 in advanced-stage atherosclerosis is unknown. Approach and Results: To investigate the effect of RIPK1 inhibition in advanced atherosclerotic plaque formation, we used ApoE SA/SA mice, which exhibit hypercholesterolemia, and develop angiotensin-II mediated hypertension upon administration of doxycycline in drinking water. These mice readily develop severe atherosclerosis, including that in coronary arteries. Eight-week-old ApoE SA/SA mice were randomized to orally receive a highly selective RIPK1 inhibitor (RIPK1i, GSK547) mixed with a western diet, or control diet. RIPK1i administration reduced atherosclerotic plaque lesion area at 2 weeks of treatment, consistent with suppressed inflammation (MCP-1, IL-1ß, TNF-α) and reduced monocyte infiltration. However, administration of RIPK1i unexpectedly exacerbated atherosclerosis at 4 weeks of treatment, concomitant with increased macrophages and lipid deposition in the plaques. Incubation of isolated macrophages with oxidized LDL resulted in foam cell formation in vitro. RIPK1i treatment promoted such foam cell formation while suppressing the death of these cells. Accordingly, RIPK1i upregulated the expression of lipid metabolism-related genes (Cd36, Ppara, Lxrα, Lxrb, Srebp1c) in macrophage foam cells with ABCA1/ABCG1 unaltered. Furthermore, RIPK1i treatment inhibited ApoA1 synthesis in the liver and reduced plasma HDL levels. Conclusion: RIPK1 modulates the development of atherosclerosis in a stage-dependent manner, implicating both pro-atherosclerotic (monocyte infiltration and inflammation) and anti-atherosclerotic effects (suppressing foam cell accumulation and promoting ApoA1 synthesis). It is critical to identify an optimal therapeutic duration for potential clinical use of RIPK1 inhibitor in atherosclerosis or other related disease indications.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34745289

RESUMO

Lianpu drink (LPD) is a traditional Chinese medicine (TCM) formula for the treatment of chronic gastritis (CG), and its clinical effects have been effectively verified. However, due to the complexity of the chemical composition of TCM formulas, its mechanism of action has not yet been clearly explained. Many studies have shown that the principal drugs in the TCM formula play a major therapeutic role. Therefore, in this study, the principal drugs Coptidis Rhizoma (CR) and Magnolia officinalis Rehd. et Wils. (MOR) in LPD were used as the main research objects to predict the mechanism of LPD on CG. We contrasted a "compounds-targets-diseases" network and screened the putative targets of CR and MOR in LPD related to CG, respectively. Furthermore, common targets of CR and MOR related to CG were selected as candidate targets. In this study, the specific target proteins of CR, MOR, and CG were combined by protein-protein interaction (PPI) to construct a pharmacological network of "components-targets-diseases." In addition, we investigated the effects of CR and MOR on the TNF signaling pathway, which mediated the remission of CG. This study preliminarily revealed that CR and MOR play a key role in the treatment of CG. Animal experiments also showed that CR and MOR could significantly improve CG by inhibiting MKK6/p38 and RIP/p38 pathway.

15.
Front Pediatr ; 9: 745687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733810

RESUMO

Background: Pediatrician workforce shortages have aroused great attention from health authorities in China. Telemedicine services have been known to enhance the management of children's health, yet the rate of adoption and usage in Chinese hospitals still at a quite low level, and the factors influencing the acceptance of telemedicine services remains unclear. Objective: The purpose of this empirical study was to evaluate the reliability and validity of a technology acceptance measurement instrument applied in healthcare, to investigate the perception of telemedicine services on the provider-side and demand-side, and to determine the factors that may drive individuals to adopt telemedicine services. Methods: A cross-sectional survey study based at Shanghai Children's Hospital, Shanghai Jiao Tong University, was conducted in March 2020. A total of 456 valid responses were obtained by convenience sampling. The internal consistency of items was assessed by Cronbach's alpha (α), composite reliability (CR) and average variance extracted (AVE) to evaluate both the reliability and validity of the questionnaire. Structural equation modeling analysis was used to test and verify the interrelationships among relevant variables. Results: Price value is the strongest predictor (ß = 0.30, p = 0.02), facilitating conditions (ß = 0.28, p = 0.01) and hedonic motivation (ß = 0.13, p = 0.04) also have significantly positive direct effects on telemedicine acceptance. The results showed the perception of child patients' families were significantly more acceptable to telemedicine services than pediatricians (t = -2.99, p < 0.01). Participants with no prior experience and lower education may be more willing to adopt telemedicine. Conclusion: Telemedicine will likely continue to have an integral role in pediatric health care delivery, and the findings can assist policy makers and hospital administrators in determining the more valued characteristics of telemedicine services from a behavioral perspective. Future attention will be paid to the pricing, training and service quality of telemedicine in China.

16.
BMJ Open ; 11(11): e052388, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785554

RESUMO

OBJECTIVES: Apolipoprotein Cs (apoCs), especially apoC-II and apoC-III, as the components of triglyceride-rich lipoproteins, play a key role in the pathophysiology of diabetes. However, prospective studies examining direct associations between apoCs and diabetes are not reproducible. The aim of this study was to evaluate the impact of apoCs on the risk of developing diabetes in a middle-aged population, and to explore possible mediators responsible for the relationship between apoCs and diabetes. DESIGN: Prospective cohort study. SETTING: Community-based study carried out in Beijing. METHODS: ApoCs were measured in 1085 participants aged 45-74 years and free of type 2 diabetes mellitus (T2DM) at baseline from the Chinese Multi-Provincial Cohort Study-Beijing Project. Multivariate logistic regression was performed to examine the association of apoCs with a 5-year risk of new-onset T2DM. The impacts of triglycerides, insulin and high-sensitivity C reactive protein (hs-CRP) on the association between apoC-III and the risk of T2DM were explored by a mediation test. RESULTS: During the 5 years of follow-up, 97 (8.9%) participants developed T2DM. ApoC-III was significantly associated with the risk of developing T2DM after multivariable adjustment (OR=1.40; 95% CI 1.07 to 1.82). This association was mainly mediated by triglyceride levels with a significant indirect effect (OR 1.61; 95% CI 1.19 to 2.18), followed by hs-CRP and insulin. CONCLUSIONS: Our findings demonstrated that higher serum apoC-III was independently associated with increased 5-year risk of new-onset T2DM in the Chinese population, and triglyceride plays a crucial role in mediating this relationship. More attention should be paid to preventive strategies of T2DM targeting apoC-III.

17.
Open Med (Wars) ; 16(1): 1718-1727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34825063

RESUMO

Mitophagy affects the activation of hepatic stellate cells (HSCs). Mitochondria-targeted ubiquinone (MitoQ) is a mitochondria-targeted antioxidant that reduces the production of intracellular reactive oxygen species (ROS). However, its relationship with mitophagy remains unclear. This study evaluated mitophagy during HSC activation and the effects of MitoQ on mitophagy in cell culture and in an animal model of the activation of HSCs. We found that MitoQ reduced the activation of HSCs and alleviated hepatic fibrosis. PINK1 (PTEN-induced putative kinase 1) is a putative serine/threonine kinase located in the mitochondria's outer membrane. While the activation of primary HSCs or LX-2 cells was associated with reduced PINK1/parkin-mediated mitophagy, MitoQ reduced intracellular ROS levels, enhanced PINK1/parkin-mediated mitophagy, and inhibited the activation of HSCs. After knocking down the key mitophagy-related protein, PINK1, in LX-2 cells to block mitophagy, MitoQ intervention failed to inhibit HSC activation. Our results showed that MitoQ inhibited the activation of HSCs and alleviated hepatic fibrosis by enhancing PINK1/parkin-mediated mitophagy.

18.
J Thorac Dis ; 13(10): 6052-6061, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34795951

RESUMO

Background: In China, the average prevalence of asthma in children aged 0-14 years increased by approximately 50% every 10 years. Hence, a specific decision support system that fits China's situation is needed for childhood asthma. This prospective, multicenter, observational study aims to assess the accuracy of the Childhood Asthma Model for Clinical Decision Support (CAMCDS) in clinical practice in four hospitals in Shanghai in China. Methods: The study will be conducted in two phases. Phase I of the study aims to evaluate the accuracy of the CAMCDS for diagnosis, while phase II of the study aims to examine the treatment predicting accuracy of the CAMCDS model. In total, 817 children diagnosed with stable asthma and 545 suspected asthma will be enrolled. The accuracy of the CAMCDS model will be calculated using the receiver operating characteristic (ROC) curve compared with the results of pediatrician's diagnosis. Besides, the treatment patterns from CAMCDS and real-world environment for Chinese children with stable asthma will be assessed, and the factors that affect the CAMCDS implementation in routine clinical practice will be explored. Conclusions: This will be the first study to examine the diagnostic accuracy and treatment predicting accuracy of a clinical decision support system in children with asthma in China. We hope that the CAMCDS will be help pediatricians in basic-level hospitals to improve the diagnosis and treatment strategy of asthma. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100045283.

19.
Biomed Eng Online ; 20(1): 111, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34794451

RESUMO

BACKGROUND: The purpose of this study was to explore whether moderate-intensity exercise can alleviate motion-induced post-traumatic osteoarthritis (PTOA) and the expression change of lncRNA H19 during this progression. METHODS: Twenty-week-old male C57BL/6 mice were randomly divided into five groups: model control group (MC group, n = 6), treadmill model group (M group, n = 6), rehabilitation control group (RC group, n = 6), treadmill model + rehabilitation training group (M + R group, n = 6) and treadmill model + convalescent group (M + C group, n = 6). Paraffin sections were used to observe the pathological changes in the mouse knee joint in each group. A micro-CT was used to scan the knee joint to obtain the morphological indexes of the tibial plateau bone. Real-time PCR was used to detect the mRNA levels of inflammatory factors, synthetic and catabolic factors in cartilage. RESULTS: After high-intensity exercise for 4 weeks, the inflammation and catabolism of the mouse knee cartilage were enhanced, and the anabolism was weakened. Further study showed that these results were partially reversed after 4-week moderate-intensity training. The results of hematoxylin-eosin staining confirmed this finding. Meanwhile, high-intensity exercise reduced the expression of lncRNA H19 in cartilage, while the expression of lncRNA H19 increased after 4 weeks of moderate-intensity exercise. CONCLUSION: High-intensity treadmill running can cause injury to the knee cartilage in C57BL/6 mice which leads to PTOA and a decrease of lncRNA H19 expression in cartilage. Moderate-intensity exercise can relieve PTOA and partially reverse lncRNA H19 expression.

20.
EMBO Rep ; : e53166, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779554

RESUMO

Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.

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