RIG-I regulates myeloid differentiation by promoting TRIM25-mediated ISGylation.

Retinoic acid-inducible gene I (RIG-I) is up-regulated during granulocytic differentiation of acute promyelocytic leukemia (APL) cells induced by all-trans retinoic acid (ATRA). It has been reported that RIG-I recognizes virus-specific 5'-ppp-double-stranded RNA (dsRNA) and activates the type I interferons signaling pathways in innate immunity. However, the functions of RIG-I in hematopoiesis remain unclear, especially regarding its possible interaction with endogenous RNAs and the associated pathways that could contribute to the cellular differentiation and maturation. Herein, we identified a number of RIG-I-binding endogenous RNAs in APL cells following ATRA treatment, including the tripartite motif-containing protein 25 (TRIM25) messenger RNA (mRNA). TRIM25 encodes the protein known as an E3 ligase for ubiquitin/interferon (IFN)-induced 15-kDa protein (ISG15) that is involved in RIG-I-mediated antiviral signaling. We show that RIG-I could bind TRIM25 mRNA via its helicase domain and C-terminal regulatory domain, enhancing the stability of TRIM25 transcripts. RIG-I could increase the transcriptional expression of TRIM25 by caspase recruitment domain (CARD) domain through an IFN-stimulated response element. In addition, RIG-I activated other key genes in the ISGylation pathway by activating signal transducer and activator of transcription 1 (STAT1), including the modifier ISG15 and several enzymes responsible for the conjugation of ISG15 to protein substrates. RIG-I cooperated with STAT1/2 and interferon regulatory factor 1 (IRF1) to promote the activation of the ISGylation pathway. The integrity of ISGylation in ATRA or RIG-I-induced cell differentiation was essential given that knockdown of TRIM25 or ISG15 resulted in significant inhibition of this process. Our results provide insight into the role of the RIG-I-TRIM25-ISGylation axis in myeloid differentiation.

Endothelial lipase promotes acute myeloid leukemia progression through metabolic reprogramming.

Metabolic reprogramming occurs in the clonal evolution of acute myeloid leukemia (AML), which contributes to cell survival under metabolic stress and the development of drug resistance. Leukemic cells exhibit various metabolic profiles, which involve multiple metabolic pathways due to the heterogeneity of AML. However, studies on metabolic targets for AML treatment are mostly focused on glycolysis at present. In this work, we established conditional knock-in AML mouse models harboring Dnmt3aR878H/WT, NrasG12D/WT, and both of the mutations, respectively. Transcriptomic analysis of Gr1+ cells from bone marrow was performed afterward to screen interested metabolic pathways and target genes. Candidate genes were studied using the CRISPR/Cas9 technique, quantitative real-time RT-PCR, and flow cytometric analyses. We revealed that multiple metabolic pathways were affected in AML mice, including lipid metabolism. Endothelial lipase (LIPG) was obviously upregulated in leukemic cells from AML mice with Dnmt3a mutation. We performed knockout of LIPG in OCI-AML3 cells carrying DNMT3A R882C mutation by using the CRISPR/Cas9 technique. Depletion of LIPG led to proliferation inhibition, apoptosis, damage of antioxidant capacity, and myeloid differentiation in OCI-AML3 cells. LIPG might serve as a potential metabolic target for the treatment of AML with abnormal lipid metabolism.

Serum adiponectin levels are reduced in autism spectrum disorder and association with severity of symptoms.

Recent evidence highlights the role of adiponectin in the pathophysiology of autism spectrum disorder (ASD), yielding conflicting results. The aims of this study were (1) To assess the adiponectin levels of children with ASD and typical developing (TP); (2) To investigate the relationship between adiponectin levels and symptom severity of children with ASD. This is a single-center cross-sectional study from China. From December 2017 to November 2019, first-diagnosis and drug-naïve children with ASD were included. Same TP children who were matched with clinical groups by gender and age were included as the control group. The enzyme-linked immunosorbent assay (ELISA) kit was used to determine serum concentrations of adiponectin. We recorded 176 children (88 were ASD and 88 were TP children) and 77.3% (n = 136) were boys and the mean age was 4.3 years (standard deviations [S.D.]: 1.2). The mean (S.D.) levels of adiponectin were 9.01(2.19) and 11.55(2.32) µg/ml for those with ASD and TP subjects. The difference between those two groups was significant (t = 7.169, p < 0.001). There was a negative correlation between serum levels of adiponectin and Childhood Autism Rating Scale [CARS] score (r = -0.498, p < 0.001). At admission, 39 ASD (54.5%) had a minor autism (CARS<37). In these children, the mean (S.D.) adiponectin level was higher than that observed in children with moderate-to-severe clinical severity (10.09[2.32] vs.8.15[1.64] µg/ml, P < 0.001). This study shows that serum adiponectin. Levels are decreased in ASD when compared with in healthy children. The findings also indicate an inverse association between serum adiponectin levels and severity of symptoms in ASD.

Conditional knockin of Dnmt3a R878H initiates acute myeloid leukemia with mTOR pathway involvement.

DNMT3A is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot DNMT3A R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged Lin-Sca1+cKit+ cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage. Consistent with leukemic cell accumulation in G2/M phase, CDK1 was up-regulated due to mTOR activation associated with DNA hypomethylation. Overexpressed CDK1-mediated EZH2 phosphorylation resulted in an abnormal trimethylation of H3K27 profile. The mTOR inhibitor rapamycin elicited a significant therapeutic response in Dnmt3aR878H/WT mice.

Long Noncoding RNA NEAT1 Promotes Myocardiocyte Apoptosis and Suppresses Proliferation Through Regulation of miR-129-5p.

Recent studies have revealed the important role of long noncoding RNAs (lncRNAs) in heart development and pathogenesis. This study was aimed to investigate the role of NEAT1 in hypoxia-induced cardiac injury and explore its possible molecular mechanism. Real-time PCR (RT-PCR) was used to determine the relative RNA expression of NEAT1 and its potential target microRNA, miR-129-5p, in the plasma of patients with acute myocardial infarction, heart failure, and angina, as well as in H2O2-treated H9c2 cells. The role of NEAT1 overexpression or inhibition in H9c2 cell migration and proliferation was assessed by transwell assay and Edu staining, respectively. Collagen deposition and apoptosis were evaluated by Western blot detection of collagen and apoptotic proteins, including Capase3, Bax, and Bcl2. We showed that H2O2 treatment significantly decreased H9c2 cell migration and proliferation while increasing H9c2 cell apoptosis. Inhibition of NEAT1 attenuated the cell apoptosis and alleviated proliferation inhibition induced by hypoxia. Bioinformatics analysis showed that miR-129-5p was the direct target of NEAT1, which was confirmed by luciferase assay. NEAT1 upregulation aggravated apoptosis by downregulating miR-129-5p. In conclusion, we uncovered a novel NEAT1-miR-129 axis and its implication in H2O2-induced heart failure.

Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008: The first nation-wide prospective multicenter study in China.

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. The trial Chinese Children Leukemia Group (CCLG)-ALL 2008 was a prospective clinical trial designed to improve treatment outcome of childhood ALL through the first nation-wide collaborative study in China. Totally 2231 patients were recruited from ten tertiary hospitals in eight cities. The patients were stratified according to clinical-biological characteristics and early treatment response. Standard risk (SR) and intermediate risk (IR) groups were treated with a modified BFM based protocol, and there was 25%-50% dose reduction during intensification phases in the SR group. Patients in high risk (HR) group received a more intensive maintenance treatment. Minimal residual disease (MRD) monitoring with treatment adjustment was performed in two hospitals (the MRD group). Complete remission (CR) was achieved in 2100 patients (94.1%). At five years, the estimate for overall survival (OS) and event-free survival (EFS) of the whole group was 85.3% and 79.9%, respectively. The cumulative incidence of relapse (CIR) was 15.3% at five years. The OS, EFS and CIR for the SR group were 91.5%, 87.9%, and 9.7%, respectively. The outcome of the MRD group is better than the non-MRD group (5y-EFS: 82.4% vs 78.3%, P = .038; 5y-CIR: 10.7% vs 18.0%, P < .001). Our results demonstrated that the large-scale multicenter trial for pediatric ALL was feasible in China. Dose reduction in the SR group could achieve high EFS. MRD-based risk stratification might improve the treatment outcome for childhood ALL.

[Multicenter Cross-sectional Community-based Nutrition Risk Screening in 3885 Chinese Elderly Adults].

Objective To evaluate the nutrition risks in Chinese elderly adults in community and provide the basis for malnutrition prevention.Methods The study population comprised of adults aged 60 years or older selected from communities. A stratified multi-stage cluster sampling method was used to investigate older adults in rural and urban areas with structured questionnaire. Nutrition Screening Initiative (NSI) checklist was used to screen nutritional status. Analyses were stratified according to age,gender,different regions,rural and urban areas,and income.Results A total of 3885 older adults with complete information were enrolled for final analyses,among whom 1894 (48.8%) were males and 1991 (51.2%) were females; 56.2% aged 60-69 years,28.8% aged 70-79 years,and 15% aged over 80 years; 1665(42.9%) were urban residents; 1592(41.0%) were in the eastern region,1211(31.2%) in the central region,and 1082(27.8%) in the western region. Up to 48.4% of the elderly adults were at high nutritional risk,and the nutritional risk was significantly higher in females (50.7%) than in males (46.0%),in individuals aged over 80 years (53.0%) than in other age groups,in urban area (41.7%) than in rural area (53.9%),and in eastern region (52.9%) than in other regions. Significant differences were found between nutritional status and the following variables: age (Χ 2=33.7,P=0.000),gender (Χ 2=15.7,P=0.000),different regions (Χ 2=72.0,P=0.000),rural and urban areas (Χ 2=69.4,P=0.000),income (Χ 2=304.9,P=0.000),and living arrangement (Χ 2=128.1,P=0.000).Conclusion Elder adults in community are at high nutritional risk.

Blocking the Interaction between EphB2 and ADDLs by a Small Peptide Rescues Impaired Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer's Disease.

Soluble amyloid-ß (Aß) oligomers, also known as Aß-derived diffusible ligands (ADDLs), are thought to be the key pathogenic factor in Alzheimer's disease (AD), but there is still no effective treatment for preventing or reversing the progression of the disease. Targeting NMDA receptor trafficking and regulation is a new strategy for early treatment of AD. Aß oligomers have been found to bind to the fibronectin (FN) type III repeat domain of EphB2 to trigger EphB2 degradation, thereby impairing the normal functioning of NMDA receptors and resulting in cognitive deficits. Here, we identified for the first time the interaction sites of the EphB2 FN domain with ADDLs by applying the peptide array method to design and synthesize four candidate peptides (Pep21, Pep25, Pep32, and Pep63) that might be able to block the EphB2-ADDL interaction. Among them, Pep63 was found to be the most effective at inhibiting the binding between EphB2 and ADDLs. We found that Pep63 not only rescued the ADDL-induced depletion of EphB2- and GluN2B-containing NMDA receptors from the neuronal surface in cultured hippocampal neurons, but also improved impaired memory deficits in APPswe/PS1dE9 (APP/PS1) transgenic mice and the phosphorylation and surface expression of GluN2B-containing NMDA receptors in cultures. Together, these results suggest that blocking the EphB2-ADDL interaction by small interfering peptides may be a promising strategy for AD treatment. SIGNIFICANCE STATEMENT: Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and amyloid ß-derived diffusible ligands (ADDLs) play a key role in triggering the early cognitive deficits that constitute AD. ADDLs may bind EphB2 and alter NMDA receptor trafficking and synaptic plasticity. Here, we identified the interaction sites of the EphB2 FN domain with ADDLs for the first time to develop a small (10 aa) peptide (Pep63) capable of blocking the EphB2-ADDL interaction. We found that Pep63 not only rescued the ADDL-induced depletion of EphB2 and GluN2B-containing NMDA receptors from the neuronal surface in cultured hippocampal neurons, but also improved impaired memory deficits in APPswe/PS1dE9 (APP/PS1) transgenic mice. Our results suggest that blocking the EphB2-ADDL interaction with Pep63 may be a promising strategy for AD treatment.

Tetrahydrofuran lignans from Viburnum betulifolium.

A phytochemical investigation of the EtOH extract from the aerial parts of Viburnum betulifolium Batal. afforded four new tetrahydrofuran lignans, betulifolium A-D (1, 2, 4, and 5), together with two known compounds vibsanol-9'-al (3) and sarcomeginal (6). This paper deals with the isolation and structure elucidation of the new compounds on the basis of spectroscopic methods, including 1D NMR, 2D NMR analyses and HR-ESI-MS data.

Effects of lead on tolerance, bioaccumulation, and antioxidative defense system of green algae, Cladophora.

Effects of various concentrations (0.5, 1.0, 2.5, 5.0, 7.5, and 10.0 mg/L) of lead (Pb(2+)) on the growth, bioaccumulation, and antioxidative defense system of green algae, Cladophora, was investigated. Low concentrations of Pb(2+) accelerated Cladophora growth, but concentrations of 10.0 mg/L and above inhibited the growth because of the hinderance to photosynthesis. The total soluble sugar content of Cladophora was affected by Pb(2+) treatment, but the protein content showed no significant changes. The malondialdehyde (MDA) content and peroxidase(POD) activity of Cladophora gradually increased whereas superoxide dismutase(SOD) decreased with Pb(2+) concentrations. Catalase (CAT) activity exhibited no significant changes following Pb(2+) treatment. Pb(2+) accumulated in Cladophora and that the lead content in Cladophora was correlated with POD growth, MDA, and Metallothionein (MT). POD and MT play a role in the survival of Cladophora in Pb-contaminated environments. This study suggests that Cladophora can be a choice organism for the phytoremediation of Pb-polluted coastal areas.

Diterpene glycosides from the ethanol extract of Diplopterygium rufopilosum.

A phytochemical investigation on the 70% EtOH extract from the dry fronds of Diplopterygium rufopilosum afforded two new labdane-type diterpene glycosides, (3ß,13S)-3-O-ß-d-glucopyranosyl-13-O-α-l-rhamnopyranosyl-labda-8(17),14-diene (1) and (3ß,13S)-3-O-α-l-rhamnopyranosyl-13-O-[6-O-acetyl-ß-d-glucopyranosyl-(1 â†’ 4)-2-O-acetyl-α-l-rhamnopyranosyl]-labda-8(17),14-diene (2). Their structures were determined on the basis of chemical method and spectroscopic analyses, including 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and HR-ESI-MS analyses.

Chemical constituents from the ethanol extract of Viburnum ternatum.

Phytochemical investigation of the 70% ethanol extract from Viburnum ternatum resulted in the isolation of three new compounds, vibsanol-9'-al (1), 4-methoxy-vibsanol (2), and 5,7-dihydroxy-4'-methoxyflavanone(8 â†’ 3')-5,7-dihydroxy-4'-methoxyflavone (4), together with a known compound vibsanol (3). Their structures were determined on the basis of spectroscopic analyses, including 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and HR-ESI-MS analyses.

The novel HLA-DRB1*14:246 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DRB1*14:246 differs from HLA-DRB1*14:18 by one nucleotide in exon 2.

Effect of peach gum polysaccharide on the rheological and 3D printing properties of gelatin-based functional gummy candy.

Excellent 3D printing materials must exhibit good extrudability and supportability, but these two characteristics are often contradictory. In this study, peach gum polysaccharide (PGP) was added to gelatin to prepare a 3D-printed functional gummy candy encapsulating curcumin. Rheology tests indicated that adding PGP could effectively improve the apparent viscosity and thermal stability and consequently improve the 3D printability and supportability of the products. When PGP addition was 6 %, the printing accuracy was higher than 90 %. Texture and microstructure analysis further revealed that PGP addition promoting a dense gel structure formed and the water holding capacity and supportability of gel materials were enhanced. Furthermore, the in vitro gastrointestinal digestion tests showed that after 6 h of simulated gastrointestinal fluid digestion, the retention rate of curcumin was nearly 80 %. The above results indicated that the composite gel of PGP and gelatin is a good 3D printing base material for nutrient delivery.

Two new rhamnopyranosides of neolignans from Sanguisorba officinalis.

Two new rhamnopyranosides of neolignans, (7S,8R)-4,9,5',9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan-7-O-α-l-rhamnopyranoside (1) and (7S,8R)-4,9,9'-trihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan-7-O-α-l-rhamnopyranoside (2), together with a known compound (7S,8R)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (3), were isolated from the 80% EtOH extract of the roots of Sanguisorba officinalis. Their structures were characterized by spectroscopic analysis including 1D NMR, 2D NMR, and HR-ESI-MS, and chemical method.

Three new amides from Microlepia pilosissima.

Phytochemical investigation of 70% EtOH extract of the dry fronds of Microlepia pilosissima has resulted in isolation of three new amides, (7E)-N-(3'-hydroxyl-4'-methoxy)-phenylethyl-4-hydroxyl-cinnamamide (1), (7E)-N-(3',4',5'-trihydroxyl)-phenylethyl-4-hydroxyl-cinnamamide (2), and (7E)-N-(3',4',5'-trihydroxyl)-phenylethyl-4-methoxy-cinnamamide (3). Their structures were characterized by spectroscopic analysis and chemical method, including 1D NMR, 2D NMR, and HR-ESI-MS.

[Gene therapy study on bladder cancer with recombinant adenoviral vector carrying LRIG1 gene driven by Survivin promoter].

OBJECTIVE: To investigate the treatment efficiency and mechanism of recombinant adenoviral vector carrying LRIG1 gene driven by Survivin promoter for bladder cancer. METHODS: Human bladder cancer cell line BIU87 and immortalized human bladder epithelial cells SV-HUC-1 were infected with Ad-Surp-LRIG1 and Ad-LRIG, respectively. The selective infection efficiency of Ad-Surp-LRIG1 and Ad-LRIG were evaluated by checking the expression of epidermal growth factor receptor (EGFR). The MTT method was used to test cell growth inhibition ratio of Ad-Surp-LRIG1 and Ad-LRIG. Heterotransplanted models of human bladder cancer cell line BIU87 cells in nude mice were established. The mice were randomly divided into 3 groups during the experiment: Ad-Surp-LRIG1 group received viral supernatant solution of Ad-Surp-LRIG1 by tail vein injection; Ad-LRIG group received viral supernatant solution of Ad-LRIG by tail vein injection; and PBS group received phosphate buffer solution (PBS). The growth of tumors were observed and the growth curve was mapped. The expression of LRIG1 and EGFR were examined by reverse transcription PCR (RT-PCR). RESULTS: When Multiplicity of infection was 25, the transfection efficiency of Ad-Surp-LRIG1 was 74.56% in BIU87 cells and 0 in SV-HUC-1 cells (χ² = 58.640, P = 0.000), while the transfection efficiency of Ad-LRIG was 68.27% in BIU87 cells and 72.52% in SV-HUC-1 cells (χ² = 0.075, P = 0.784). The transfection efficiency difference of Ad-Surp-LRIG1 and Ad-LRIG in BIU87 cells was not statistically significant (χ² = 0.016, P = 0.898). Compared with PBS, Ad-Surp-LRIG1 and Ad-LRIG1 could inhibit BIU87 cell growth, the difference was significant in 4 days after transfection (F = 15.960, P = 0.000). There was not significant difference in cell growth rate of Ad-Surp-LRIG1 group and Ad-LRIG1 group. The tumor growth rate in Ad-Surp-LRIG1 group was slower than that in the other 2 groups. The tumor quality in Ad-Surp-LRIG1 was lighter than that in the other two groups, the differences were statistically significant (F = 97.860, P = 0.000), the quality difference in Ad-LRIG1 group and PBS group was not statistically significant difference (t = 1.73, P = 0.06). Compared with Ad-LRIG1 group and PBS group, the mRNA expression of LRIG1 was obviously up-regulated and that of EGFR was down-regulated in Ad-Surp-LRIG1 group (P < 0.01). CONCLUSIONS: The recombinant adenoviral vector of Ad-Surp-LRIG1 could selectively transfected BIU87 cells, which could inhibit significantly the growth of bladder cancer in vivo and in vitro, the mechanism may be partly LRIG1 can downgrade the expression of EGFR.

Clinical Features of Urticaria: Results From a Hospital-Based Multicenter Study in China.

Background: The clinical features of urticaria have not been fully illustrated. Objectives: To demonstrate clinical features of urticaria in different areas of southern and northern China. Methods: In this hospital-based multicenter study, outpatients with urticaria filled in a questionnaire during the initial visit and follow-up (once per week, lasting for a month). Results: Overall, 1,715 outpatients with urticaria with a mean age of 37.86 ± 16.08 years (range = 0.5-87 years) were recruited. The median disease duration was 1.94 ± 4.31 years (range = 0-58 years). More itching was observed in the northern areas higher than that in the southern areas (99.5 vs 94.1%, P < 0.001). The incidence of pain, arthralgia, and family history in southern areas was higher than that in northern areas (5.1 vs 1.1%, 9.6 vs 0, 10.6% vs 3.2%, P < 0.001). The leading subtypes of specified urticaria were chronic spontaneous urticaria (81.4%) and symptomatic dermographism (35.9%). The incidence of symptomatic dermographism and cold urticaria in the southern areas was lower than that in the northern areas (31.8 vs. 50.3%, 4 vs. 8.5%, P < 0.001). Allergic diseases were the most common concomitant disorders of urticaria. More than half of the patients had to avoid certain food, such as fish-prawn-crab (30.7%) and alcohol (20%). Ebastine (41.1%) was the most commonly prescribed drug. The disease duration negatively correlated with the severity of itching and number of wheals (>50/24H) (Spearman's rank correlation test, p < 0.001). Conclusion: This study provides a profile of clinical characteristics of urticaria in China and filled the gap in the field of regional comparative studies on urticaria.

Leonurine Attenuates Obesity-Related Vascular Dysfunction and Inflammation.

Oxidative stress in adipose tissue is a crucial pathogenic mechanism of obesity-associated cardiovascular diseases. Chronic low-grade inflammation caused by obesity increases ROS production and dysregulation of adipocytokines. Leonurine (LEO) is an active alkaloid extracted from Herba Leonuri and plays a protective role in the cardiovascular system. The present study tested whether LEO alleviates inflammation and oxidative stress, and improves vascular function in an obese mouse model. Here, we found that obesity leads to inflammation and oxidative stress in epididymal white adipose tissue (EWAT), as well as vascular dysfunction. LEO significantly improved inflammation and oxidative stress both in vivo and in vitro. Obesity-induced vascular dysfunction was also improved by LEO as evidenced by the ameliorated vascular tone and decreased mesenteric artery fibrosis. Using mass spectrometry, we identified YTHDF1 as the direct target of LEO. Taken together, we demonstrated that LEO improves oxidative stress and vascular remodeling induced by obesity and targets YTHDF1, raising the possibility of LEO treating other obesity-related metabolic syndromes.

Icariin represses the inflammatory responses and survival of rheumatoid arthritis fibroblast-like synoviocytes by regulating the TRIB1/TLR2/NF-kB pathway.

BACKGROUND: Effective treatment methods for rheumatoid arthritis (RA) are still lacking. Previous studies have shown that icariin exerts a significant therapeutic effect on RA; however, the molecular mechanism requires further analysis. METHODS: qRT-PCR and western blot were performed to examine the gene or protein levels, respecctively. The proinflammatory cytokine levels were determined utilizing ELISA and western blot assays. Cell proliferation and apoptosis were quantified using CCK-8, EdU and flow cytometry assays, respectively. A RA mouse model was established to observe histopathological changes. RESULTS: Both icariin treatment and TRIB1 overexpression inhibited proliferation and inflammatory responses but promoted the apoptosis of TNF-α-treated RA-FLSs. Icariin treatment increased TRIB1 expression by promoting Nrf2 expression, thus blocking TLR2/NF-κB signalling. In addition, functional rescue experiments suggested that TRIB1 knockdown strikingly restrained the biological effects of icariin on TNF-α-treated RA-FLSs. Moreover, in vivo experimental results revealed that icariin restored inflammation and deterioration in RA mice by upregulating TRIB1. CONCLUSIONS: Based on these results, icariin repressed TNF-α-induced inflammatory responses and survival in RA-FLSs by regulating the TRIB1/TLR2/NF-kB pathway, implying that icariin may be a promising candidate drug for RA treatment.