Effects of botulinum toxin type A in patients with painful temporomandibular joint disorders: a systematic review and meta-analysis.

Objective: To assess the therapeutic efficacy of botulinum toxin type A (BTX-A) for managing myofascial pain related to temporomandibular disorders (TMDs). Methods: This study was conducted according to the PRISMA 2020 statement guidelines. The PubMed, Embase, and Cochrane Library databases were searched. Only randomized controlled trials were included. The primary outcome was a pain score on the visual analog scale, and the secondary outcomes were maximum mouth opening and adverse effects. The Cochrane risk of bias tool was used to assess risk bias. A meta-analysis of studies with the same interventions, controls, assessment methods, and follow-up durations was performed. Results: A total of 519 studies were retrieved, of which 20 randomized controlled trials were included in the qualitative analysis and six were included in the meta-analysis. The results showed that, compared with placebo, BTX-A injection was more effective at relieving myofascial pain, and its effect was similar to that of conventional methods. However, there was no difference in maximum mouth opening between the two groups. After the study assessment with the RoB 2.0 tool, six studies showed a low risk of bias, 13 studies showed some concerns regarding the reported results, and only one study showed a high risk of bias. Adverse effects of BTX-A injection were observed in four studies. Conclusions: In conclusion, BTX-A is effective at relieving pain in TMD patients but does not improve mouth opening. To minimize adverse effects, we recommend a low dose of BTX-A for TMD patients who do not experience complete pain relief from conservative treatments.

Prognostic signature based on S100 calcium-binding protein family members for lung adenocarcinoma and its clinical significance.

The S100 family proteins (S100s) participate in multiple stages of tumorigenesis and are considered to have potential value as biomarkers for detecting and predicting various cancers. But the role of S100s in lung adenocarcinoma (LUAD) prognosis is elusive. Transcriptional data of LUAD patients were retrieved from TCGA, and relevant literature was extensively reviewed to collect S100 genes. Differential gene expression analysis was performed on the LUAD data, followed by intersection analysis between the differentially expressed genes (DEGs) and S100 genes. Unsupervised consensus clustering analysis identified two clusters. Significant variations in overall survival between the two clusters were shown by Kaplan-Meier analysis. DEGs between the two clusters were analyzed using Lasso regression and univariate/multivariate Cox regression analysis, leading to construction of an 11-gene prognostic signature. The signature exhibited stable and accurate predictive capability in TCGA and GEO datasets. Subsequently, we observed distinct immune cell infiltration, immunotherapy response, and tumor mutation characteristics in high and low-risk groups. Finally, small molecular compounds targeting prognostic genes were screened using CellMiner database, and molecular docking confirmed the binding of AMG-176, Estramustine, and TAK-632 with prognostic genes. In conclusion, we generated a prognostic signature with robust and reliable predictive ability, which may provide guidance for prognosis and treatment of LUAD.

Loss of ß-arrestin2 aggravated condylar cartilage degeneration at the early stage of temporomandibular joint osteoarthritis.

OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disorder characterized by extracellular matrix degeneration and inflammatory response of condylar cartilage. ß-arrestin2 is an important regulator of inflammation response, while its role in TMJOA remains unknown. The objective of this study was to investigate the role of ß-arrestin2 in the development of TMJOA at the early stage and the underlying mechanism. METHODS: A unilateral anterior crossbite (UAC) model was established on eight-week-old wild-type (WT) and ß-arrestin2 deficiency mice to simulate the progression of TMJOA. Hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis were used for histological and radiographic assessment. Immunohistochemistry was performed to detect the expression of inflammatory and degradative cytokines, as well as autophagy related factors. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay was carried out to assess chondrocyte apoptosis. RESULTS: The loss of ß-arrestin2 aggravated cartilage degeneration and subchondral bone destruction in the model of TMJOA at the early stage. Furthermore, in UAC groups, the expressions of degradative (Col-X) and inflammatory (TNF-α and IL-1ß) factors in condylar cartilage were increased in ß-arrestin2 null mice compared with WT mice. Moreover, the loss of ß-arrestin2 promoted apoptosis and autophagic process of chondrocytes at the early stage of TMJOA. CONCLUSION: In conclusion, we demonstrated for the first time that ß-arrestin2 plays a protective role in the development of TMJOA at the early stage, probably by inhibiting apoptosis and autophagic process of chondrocytes. Therefore, ß-arrestin2 might be a potential therapeutic target for TMJOA, providing a new insight for the treatment of TMJOA at the early stage.

Enhanced Magnetoimpedance Effect in Co-Based Micron Composite CoFeNiSiB Ribbon Strips Coated by Carbon and FeCoGa Nanofilms for Sensing Applications.

Quenched Co-based ribbon strips are widely used in the fields of magnetic amplifier, magnetic head material, magnetic shield, electric reactor, inductance core, sensor core, anti-theft system label, and so on. In this study, Co-based composite CoFeNiSiB ribbon strips with a micron width were fabricated by micro-electro-mechanical systems (MEMS) technology. The carbon and FeCoGa nanofilms were deposited for surface modification. The effect of carbon and FeCoGa nanofilm coatings on the crystal structure, surface morphology, magnetic properties, and magnetoimpedance (MI) effect of composite ribbon strips were systematically investigated. The results show that the surface roughness and coercivity of the composite ribbon strips are minimum at a thickness of the carbon coating of 60 nm. The maximum value of MI effect is 41% at 2 MHz, which is approximately 2.4 times greater than plain ribbon and 1.6 times greater than FeCoGa-coated composite ribbon strip. The addition of a carbon layer provides a conductive path for high frequency currents, which effectively reduces the characteristic frequency of the composite ribbon strip. The FeCoGa coating is able to close the flux path and reduce the coercivity, which, in turn, increases the transverse permeability and improves the MI effect. The findings indicate that a successful combination of carbon layer and magnetostrictive FeCoGa nanofilm layer can improve the MI effect and magnetic field sensitivity of the ribbon strips, demonstrating the potential of the composite strips for local and micro area field sensing applications.

Reciprocal polarization imaging of optical activity in reflection.

We present reciprocal polarization imaging for the optical activity of chiral media in reflection geometry. The method is based on the reciprocal polar decomposition of backscattering Mueller matrices accounting for the reciprocity of light waves in forward and backward scattering paths. Anisotropic depolarization is introduced to gain sensitivity to optical activity in backscattering. Experiments with glucose solutions show that while the Lu-Chipman decomposition of the backscattering Mueller matrices produces erroneous results, reciprocal polarization imaging correctly retrieves the optical activity of chiral media. The recovered optical rotation agrees with that obtained in the forward geometry and increases linearly with the concentration and thickness of the chiral media. The potential for in vivo glucose monitoring based on optical activity sensing using reciprocal polarization imaging is then discussed.

The P38MAPK/ATF2 signaling pathway is involved in PND in mice.

Accumulating evidence indicates that microglia-mediated neuroinflammation in the hippocampus contributes to the development of perioperative neurocognitive disorder (PND). P38MAPK, a point of convergence for different signaling processes involved in inflammation, can be activated by various stresses. This study aims to investigate the role of the P38MAPK/ATF2 signaling pathway in the development of PND in mice. Aged C57BL/6 mice were subjected to tibial fracture surgery under isoflurane anesthesia to establish a PND animal model. The open field test was used to evaluate the locomotor activity of the mice. Neurocognitive function was assessed with the Morris water maze (MWM) and fear conditioning test (FCT) on postoperative days 1, 3 and 7. The mice exhibited cognitive impairment accompanied by increased expression of proinflammatory factors (IL-1ß, TNF-α), proapoptotic molecules (caspase-3, bax) and microglial activation in the hippocampus 1, 3 and 7 days after surgery. Treatment with SB239063 (a P38MAPK inhibitor) decreased the expression of proinflammatory factors, proapoptotic molecules and Iba-1 in the CA1 region of the hippocampus. The number of surviving neurons was significantly increased. Inhibition of the P38MAPK/ATF2 signaling pathway attenuates hippocampal neuroinflammation and neuronal apoptosis in aged mice with PND, thus improving the perioperative cognitive function of the mice.

Facile construction of nanocubic Mn3[Fe(CN)6]2@Pt based electrochemical DNA sensors for ultrafast precise determination of SARS-CoV-2.

Owing to the high mortality and strong infection ability of COVID-19, the early rapid diagnosis is essential to reduce the risk of severe symptoms and the loss of lung function. In clinic, the commonly used detection methods, including the computed tomography (CT) and reverse transcription-polymerase chain reaction (RT-PCR), are often time-consuming with bulky instruments, which normally require more than one hour to report the results. To shorten the analytical period for testing the COVID-19 virus (SARS-CoV-2), we proposed an ultrafast and ultrasensitive DNA sensors to achieve an accurate determination of the DNA sequence by the RNA reverse transcription (rtDNA) of the SARS-CoV-2. A nanocubic architecture of the MnFe@Pt crystals was constructed to integrate both electrocatalysis and conductivity to greatly improve the biosensing performance. After the immobilization of a specific capture and report DNA on above nanocomposite, the rtDNA can be rapidly caught to the DNA sensor to form a double-helix structure, thus generating the current signal change. Within only 10 min, the as-prepared DNA sensors exhibited ultralow detection limit (1 × 10-20 M) and wide linear detection range, together with an outstanding selectivity among various interfering substances.

Microcystin-LR prenatal exposure drives preeclampsia-like changes in mice by inhibiting the expression of TGF-ß and VEGFA.

Microcystin-leucine-arginine (MC-LR) is widespread in the water and food, which has suspected to be associated with adverse pregnancy outcomes. In the present study, we aim to assess the interaction between MC-LR exposure and preeclampsia development and elucidate the molecular events involved. After exposure to MC-LR during pregnancy, the mice developed hypertension and proteinuria, the typical symptoms of preeclampsia. This was associated with decreased invasiveness of placental trophoblast and vascular dysplasia caused by MC-LR through down-regulating VEGFA and TGF-ß expression via AKT/m-TOR/HIF-1α pathway. In addition, this conclusion has been confirmed in a case-control study. Significantly, the addition of Deferoxamine (DFM), a phosphorylated serine-threonine protein kinases (p-AKT) specific agonist, can antagonize the inhibitory effect of MC-LR on the expression of related proteins, which further ameliorate the migration and invasion ability of HTR-8/Svneo cells. To sum up, our study revealed the pathologic mechanism by which MC-LR lead to preeclampsia and emphasized the importance of pregnancy management.

Coordination effect enhanced visualization of latent fingerprint with Eu (TTA)3phen-SiO2 microspheres.

Latent fingerprint (LFP) powders are crucial in the detection of LFPs in forensic science. However, it is often plagued by poor image resolution and low contrast. Herein, enhanced LFP fluorescence (FL) visualizations are achieved by doping Eu(III) coordination compound Eu(TTA)3phen directly into SiO2 microspheres instead of Eu(III) ions. Using the synthesized Eu(TTA)3phen-SiO2 microspheres, the fine characteristic structure of LFP can be seen and recognized under 365 nm irradiation, up to Level 3. However, the Eu3+-SiO2 microspheres were difficult to recognize the Level 2,3 fingerprint structure. The difference between the ridge and furrow gray values of Eu(TTA)3phen-SiO2 microspheres is 2.1 times that of Eu3+-SiO2 microspheres. The coordination effect increased the asymmetry around Eu(III) ions, resulting in the ultrasensitive 5D0→7F2 transition, thus increasing the FL intensity, and the uniform doping of the Eu(III) coordination compound into SiO2 also reduced the surface FL quenching due to shielding from oxygen. Under this dual effect, the LFP performance of Eu(TTA)3phen-SiO2 microspheres has been significantly improved. We believe that this novel and easy LFP visualization method is a promising routine in specific target detection including criminal investigation, customhouse check-in, and drug control.

Optimizing Levilactobacillus brevis NPS-QW 145 Fermentation for Gamma-Aminobutyric Acid (GABA) Production in Soybean Sprout Yogurt-like Product.

Gamma-aminobutyric acid (GABA) is a non-protein amino acid with various physiological functions. Levilactobacillus brevis NPS-QW 145 strains active in GABA catabolism and anabolism can be used as a microbial platform for GABA production. Soybean sprouts can be treated as a fermentation substrate for making functional products. This study demonstrated the benefits of using soybean sprouts as a medium to produce GABA by Levilactobacillus brevis NPS-QW 145 when monosodium glutamate (MSG) is the substrate. Based on this method, a GABA yield of up to 2.302 g L-1 was obtained with a soybean germination time of one day and fermentation of 48 h with bacteria using 10 g L-1 glucose according to the response surface methodology. Research revealed a powerful technique for producing GABA by fermentation with Levilactobacillus brevis NPS-QW 145 in foods and is expected to be widely used as a nutritional supplement for consumers.

MiR-137 targets and regulates E2F7 to suppress progression of glioma cells.

INTRODUCTION: The paper aimed to explore the mechanism of miR-137 in modulating glioma. MATERIAL AND METHODS: qRT-PCR detected miR-137 and E2F7 mRNA expression in cells. The protein expression of E2F7 was measured using Western blot assay. Cell proliferation, scratch healing, transwell and programmed cell death assays were conducted to examine the influences of the genes on the biological function of glioma cells. The dual-luciferase assay verified the interaction between miR-137 and E2F7. RESULTS: MiR-137 was lowly expressed in glioma cells, and E2F7 was highly expressed. MiR-137 suppressed progression and promoted programmed cell death of glioma cells. MiR-137 could target and negatively regulate E2F7 expression to further accelerate programmed cell death of glioma cells. CONCLUSIONS: It was found that miR-137 could target E2F7 to restrain cell progression and accelerate programmed cell death of glioma cells, which is helpful to search for new molecular therapeutic targets for glioma.

Microcystin-LR inhibits early pregnancy by impairing the vascular network of luteum: Involvement of the MEK/ERK/SP1/VEGFR2 axis.

Microcystin-leucine-arginine (MC-LR) reduces the fertility of female mice, but the mechanism is unknown. We studied the effect of MC-LR on early pregnancy and elucidated its possible mechanism. The number of embryo beds and embryo volume decreased in pregnant mice at 6 or 8 days after fertilization after acute exposure to MC-LR. The corpus luteum secretes estrogen and progesterone, which are involved in embryo implantation and maintenance of early pregnancy. MC-LR exposure reduced luteal blood vessel branches and inhibited hormone synthesis. Functional blood vessels are essential to the maintenance of luteal structure and function. Reduced migration and tube-forming were also detected in human umbilical vascular endothelial cells (HUVECs) treated with MC-LR. MC-LR significantly decreased the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in vivo and in vitro, which was responsible for the inhibited construction of the vascular network. The MEK/ERK/SP1 signal pathway mediated the decrease in VEGFR2 expression, and the agonists of phosphorylated extracellular regulated protein kinases (p-ERK) alleviated the anti-angiogenic effect of MC-LR. In conclusion, we demonstrated the toxicity of MC-LR on construction of vascular network in corpus luteum, which could provide a new perspective on female infertility or miscarriage caused by environmental factors.

Wall-associated kinase-like gene RL1 contributes to red leaves in sorghum.

Red leaves are common in trees but rare in cereal crops. Red leaves can be used as raw materials for anthocyanin extraction and may have some adaptive significance for plants. In this study, we discovered a red leaf phenotype in the F1 hybrids derived from a cross between two sorghum accessions with green leaf. Histological analysis of red leaves and green leaves showed that red compounds accumulate in mesophyll cells and gradually spreads to the entire leaf blade. In addition, we found chloroplasts degraded more quickly in red leaves than in green leaves based on transmission electron microscopy. Metabolic analysis revealed that flavonoids including six anthocyanins are more abundant in red leaves. Moreover, transcriptome analysis revealed that expression of flavonoid biosynthesis genes was upregulated in red leaves. These observations indicate that flavonoids and anthocyanins in particular, are ideal candidates for the red compounds accumulating in red leaves. Segregation analysis of the red leaf phenotype suggested a genetic architecture consisting of three dominant genes, one (RL1 for RED LEAF1) of which we mapped to a 55-kb region on chromosome 7 containing seven genes. Sequencing, reverse transcription-polymerase chain reaction, and transcriptome analysis suggested Sobic.007G214300, encoding a wall-associated kinase, as the most likely candidate for RL1. Fine mapping the red leaf gene and identifying the metabolites that cause red leaf in sorghum provide us with a better understanding of the red leaf phenotype in the natural population of sorghum.

AADAC promotes therapeutic activity of cisplatin and imatinib against ovarian cancer cells.

OBJECTIVE: To explore how AADAC functions in the malignant progression of ovarian cancer, and the effect of AADAC on drug therapeutic activity against ovarian cancer cells. METHODS: AADAC level in tumor and normal samples from TCGA-OV dataset and its survival significance were analyzed by bioinformatics methods. Signaling pathway enrichment analysis for the high- and low-AADAC patients was achieved by using GSEA software. AADAC expression in the cell lines with different treatments was evaluated via qRT-PCR. Cell proliferative ability was assessed via MTT assay Cell migratory and invasive abilities were evaluated via transwell assay. Angiogenesis assay was performed to examine the angiogenetic ability. RESULTS: AADAC was upregulated in ovarian cancer tissues, and patients with high expression of AADAC had favorable survival conditions compared to the low AADAC expression ones. Overexpression of AADAC inhibited the malignant progression of ovarian cancer cells. Both cisplatin and imatinib suppressed cancer cell malignant progression, while overexpressed AADAC synergistically enhanced such inhibition. CONCLUSIONS: The study demonstrated that AADAC could somehow suppress the malignant progression of ovarian cancer, especially at the cellular level. In addition, synergic tumor-inhibitory effects between AADAC and the anti-cancer drugs were identified. All the above results proposed a novel idea and candidate biomarker for ovarian cancer therapy.

miR-218-5p inhibits the malignant progression of glioma via targeting TCF12.

Several studies have shown the ability of transcription factor 12 (TCF12) to promote tumor malignant progression, but its function in glioma cells has not been fully elucidated. In this study, we analyzed the data from TCGA by bioinformatics and found that in glioma tissue, TCF12 was conspicuously highly expressed while miR-218-5p was significantly low-expressed. The downregulation of miR-218-5p was correlated with adverse prognosis in patients with glioma. miR-218-5p was found to be negatively associated with TCF12 by Pearson correlation analysis, and dual luciferase assay was employed to verify that miR-218-5p and TCF12 had a targeting relationship. qRT-PCR and Western blot assays were used to verify that the expression of TCF12 was regulated by its upstream regulator miR-218-5p. Moreover, cell experiments validated that overexpressed TCF12 could promote the proliferation, migration, and invasion of glioma cells and inhibit their apoptosis, whereas overexpressing miR-218-5p at the same time could reverse this phenomenon. Our study demonstrates the regulatory mechanism of the miR-218-5p/TCF12 axis in gliomas, which lays a foundation for searching for new therapeutic approaches for glioma.

Exosomes Derived from Cancer-Associated Fibroblasts Regulate Cell Progression in Clear-Cell Renal-Cell Carcinoma.

BACKGROUNDS: Exosomes from multiple sources function as regulatory factors in progression of various tumors. However, studies on the impact of exosomes from cancer-associated fibroblasts (CAFs) on tumor-cell proliferation, migration, invasion, and cycle regulation in clear-cell renal-cell carcinoma (ccRCC) are still lacking. METHODS: A Western blot assay was performed to test the exosome-related marker protein level in exosomes derived from CAFs and normal fibroblasts (NFs). A confocal microscope was utilized to observe the internalization of CAF- and NF-derived exosomes after coculturing with cancer cells. MTT, EdU, colony formation, and transwell assays were conducted to detect progression of cancer cells incubated with CAF-derived exosomes. A Western blot assay was also conducted to test expression levels of metastasis-associated proteins. Changes in cell apoptosis and cell cycle were measured by flow cytometry. RESULTS: Expression of CAF-derived exosome-related marker proteins was higher than that from NFs. Exosomes derived from CAFs and NFs could enter into cancer cells smoothly and be internalized by cancer cells. After cancer cells were cocultured with CAF-derived exosomes, cell proliferation, migration, and invasion were notably enhanced, and cell apoptosis was reduced. Moreover, expression of fibronectin, N-cadherin, vimentin, MMP9, and MMP2 in cancer cells increased, while E-cadherin was decreased. Besides, the proportion of cancer cells in the S phase increased. CONCLUSION: CAF-derived exosomes are internalized into ccRCC cells and promote the progression of ccRCC.

LOXL2 attenuates osteoarthritis through inactivating Integrin/FAK signaling.

Temporomandibular joint OA (TMJOA) is a common degenerative joint disease, leads to structural damage and ultimately loss of function. Matrix degradation is one of the first pathogenesis during the progression of OA, it was effective to inhibit matrix degradation to block the development of OA. In this study, an in vivo model (compressive mechanical force) and an in vitro model (IL-1ß) were used to induce OA-like changes in TMJ cartilage and chondrocytes. We revealed lysyl oxidase like-2 (LOXL2) play a critical role in TMJOA. LOXL2 expression decreased in mechanical stress/IL-ß induced TMJOA-like lesions in both in vivo models and in vitro models. Furthermore, recombinant LOXL2 (rhLOXL2) treatment ameliorated the degenerative changes induced by mechanical stress in vivo, including the thinning cartilage, down-expression of collagen II and proteoglycan, and over-expression of TNF-a, while LOXL2 antibody (anti-LOXL2) treatment exacerbated these changes. Mechanistically, the protection of LOXL2 in chondrocytes was induced partly through activation of the Integrin/FAK pathway. The inhibition of the Integrin/FAK pathway could neutralized the effects caused by rhLOXL2. Collectively, our study suggests that the LOXL2 plays a protective role in mechanical stress induced TMJOA-like changes, and the Integrin/FAK pathway may be a key downstream pathway in this process.

MiR-433-3p restrains the proliferation, migration and invasion of glioma cells via targeting SMC4.

OBJECTIVE: Glioma is a common primary malignant brain tumor characterized by high mortality and poor prognosis. The purpose of this study is to explore the molecular mechanism underlying glioma, aiming to provide a new target for the treatment of glioma to improve the prognosis of patients. METHODS: The differentially expressed genes and regulatory axis affecting the prognosis of glioma were identified with bioinformatics analysis, and the expression of miR-433-3p and SMC4 mRNA was detected with qRT-PCR. The expression of SMC4 and epithelial-mesenchymal transition (EMT)-associated proteins were detected with western blot. The targeting relationship between miR-433-3p and SMC4 was verified with dual-luciferase reporter gene assay. The proliferative ability of glioma cells was detected with CCK-8 assay, while the migration and invasion of glioma cells were detected with Transwell assay. RESULTS: We found that the expression of SMC4 was significantly up-regulated in glioma, showing that SMC4 was an unfavorable factor for prognosis and could promote the progression of cancer cells. Its upstream regulator miR-433-3p was significantly down-regulated in glioma, which inhibited the development of cancer cells. Moreover, miR-433-3p could target to inhibit the expression of SMC4. Rescue assay showed that miR-433-3p could affect the development of glioma by regulating the expression of SMC4. CONCLUSION: Our data demonstrate for the first time that SMC4 is a direct target of miR-433-3p, and elucidate the molecular mechanism by which miR-433-3p inhibits the malignant progression of glioma by targeting and down-regulating the expression of SMC4.

Ligand Non-innocence and Single Molecular Spintronic Properties of AgII Dibenzocorrole Radical on Ag(111).

A facile method for the quantitative preparation of silver dibenzo-fused corrole Ag-1 is described. In contrast to the saddle conformation resolved by single-crystal X-ray analysis for Ag-1, it adopts an unprecedented domed geometry, with up and down orientations, when adsorbed on an Ag(111) surface. Sharp Kondo resonances near Fermi level, both at the corrole ligand and the silver center were observed by cryogenic STM, with relatively high Kondo temperature (172 K), providing evidence for a non-innocent AgII -corrole.2- species. Further investigation validates that benzene ring fusion and molecule-substrate interactions play pivotal roles in enhancing Ag(4d(x2 -y2 ))-corrole (π) orbital interactions, thereby stabilizing the open-shell singlet AgII -corrole.2- on Ag(111) surface. Moreover, this strategy used for constructing metal-free benzene-ring fused corrole ligand gives rise to inspiration of designing novel metal-corrole compound for multichannel molecular spintronics devices.

BRD4 inhibition alleviates mechanical stress-induced TMJ OA-like pathological changes and attenuates TREM1-mediated inflammatory response.

The aim of this paper was to investigate the protective effects of bromodomain containing 4 (BRD4) inhibition on the temporomandibular joint osteoarthritis (TMJ OA) induced by compressive mechanical stress and to explore the underlying mechanism. In vivo, a rat model of TMJ compressive loading device was used and BRD4 inhibitor was injected into the TMJ region. HE staining and micro-CT analysis were used for histological and radiographic assessment. Immunohistochemistry and qPCR were performed to detect inflammatory cytokines expressions. High-throughput ChIP-sequencing screening was performed to compare the BRD4 and H3K27ac binding patterns between condylar cartilage from control and mechanical force groups. In vitro, the mandibular condylar chondrocytes were treated with IL-1ß. Small Interference RNA (siRNA) infection was used to silencing BRD4 or TREM1. qPCR was performed to detect inflammatory cytokines expressions. Our study showed that BRD4 inhibition can alleviate the thinning of condylar cartilage and subchondral bone resorption, as well as decrease the inflammatory factors expression both in vivo and in vitro. ChIP-seq analysis showed that BRD4 was more enriched in the promoter region of genes related to the stress and inflammatory pathways under mechanical stress in vivo. Trem1, a pro-inflammatory gene, was screened out from the overlapped BRD4 and H3K27ac increased binding sites, and Trem1 mRNA was found to be regulated by BRD4 inhibition both in vivo and in vitro. TREM1 inhibition reduced the expression of inflammatory factors induced by IL-1ß in vitro. In summary, we concluded that BRD4 inhibition can protect TMJ OA-like pathological changes induced by mechanical stress and attenuate TREM1-mediated inflammatory response.