Salidroside suppresses cell growth and inflammatory response of fibroblast-like synoviocytes via inhibition of phosphoinositol-3 kinase/threonine kinase signaling in rheumatoid arthritis.

BACKGROUND: Salidroside (Sal) is a natural product commonly isolated from Rhodiola rosea L., which has been found to have numerous pharmacological activities (e.g., ameliorating apoptosis and inflammation, and acting as an antioxidant) in various diseases, but its concrete function in rheumatoid arthritis (RA) has not been revealed yet. Here, we aimed to explore the specific role and underlying mechanisms of Sal in RA-fibroblast-like synoviocytes (RA-FLSs). METHODS: Cell counting kit 8 (CCK-8) was used to assess the viability of normal-FLSs and RA-FLSs. Cell apoptosis in RA-FLSs was evaluated by flow cytometry. Western blotting was prepared to examine the levels of apoptosis- and signaling-related proteins. Wound-healing and Transwell assays were conducted to examine RA-FLSs migration and invasion. Enzyme-linked immunosorbent assay (ELISA) was used to assess the effect of Sal on tumor necrosis factor-alpha (TNF-α)-induced inflammation in RA-FLSs. RA animal model was established through complete Freund's adjuvant (CFA) induction, and the histopathological changes in synovial tissues of the rat model were analyzed by H&E staining. RESULTS: RA-FLSs were treated with 200 µM Sal for 24 h, and cell viability was significantly suppressed. Sal promoted RA-FLSs apoptosis. The migratory and invasive abilities of RA-FLSs were markedly inhibited by Sal. Sal incubation reduced the levels of inflammatory cytokines interleukin­8 (IL-8), IL-1ß, and IL­6 in RA-FLSs under the stimulation of TNF­α. Subsequently, Sal downregulated phosphorylated phosphatidylinositol­3 kinase (p-PI3K) and protein kinase (p-AKT) expression in RA-FLSs. After the treatment with pathway activator 740Y­P (20 µM) in RA-FLSs, the promotive effect of Sal on cell apoptosis was reversed, and inhibitory effects of it on cell viability, migration, invasion, and inflammatory response were abolished. Sal inhibited RA development in the CFA-induced rat model. CONCLUSION: Sal suppressed cell growth and inflammation in RA-FLSs by inactivating PI3K/AKT-signaling pathways.

Diagnostic performance of D-dimer in predicting pulmonary embolism in tuberculous pleural effusion patients.

BACKGROUND: Tuberculous pleural effusion (TPE) patients usually have elevated D-dimer levels. The diagnostic performance of D-dimer in predicting pulmonary embolism (PE) in the TPE population is unclear. This study aimed to assess the diagnostic performance of D-dimer for PE in the TPE population and explore its potential mechanism. METHODS: We retrospectively analysed patients who were admitted to Xinhua Hospital and Weifang Respiratory Disease Hospital with confirmed TPE between March 2014 and January 2020. D-dimer levels were compared between patients with and without PE. To test the diagnostic performance of D-dimer in predicting PE, receiver operating characteristic curve analysis was performed. Positive predictive value (PPV) and negative predictive value (NPV) were also reported. To explore the potential mechanism of PE in TPE, inflammatory biomarkers were compared between PE and non-PE patients. RESULTS: This study included 248 patients (170 males and 78 females) aged 43 ± 20.6 years. Elevated D-dimer levels (≥ 0.5 mg/L) were detected in 186/248 (75%) patients. Of the 150 patients who underwent computed tomography pulmonary angiography, 29 were diagnosed with PE. Among the TPE population, the PE patients had significantly higher D-dimer levels than the non-PE patients (median, 1.06 mg/L vs. 0.84 mg/L, P < 0.05). The optimal cut-off value for D-dimer in predicting PE in TPE was 1.18 mg/L, with a sensitivity of 89.7% and a specificity of 77.8% (area under curve, 0.893; 95% confidence interval 0.839-0.947; P < 0.01). The PPV was 49.1%, while the NPV was 96.9% at a D-dimer cut-off of 1.18 mg/L for PE. PE patients had lower median WBC and interleukin (IL)-8 values (5.14 × 109/L vs. 6.1 × 109/L, P < 0.05; 30.2 pg/ml vs. 89.7 pg/ml, P < 0.05) but a higher median IL-2 receptor value (1964.8 pg/ml vs. 961.2 pg/ml, P < 0.01) than those in the non-PE patients. CONCLUSIONS: D-dimer is an objective biomarker for predicting PE in patients with TPE. A D-dimer cut-off of 1.18 mg/L in the TPE population may reduce unnecessary radiological tests due to its excellent sensitivity, specificity, and NPV for PE. The imbalance of prothrombotic and antithrombotic cytokines may partly be attributed to the formation of pulmonary emboli in patients with TPE.

EPAS1 regulates proliferation of erythroblasts in chronic mountain sickness.

Excessive erythrocytosis (EE) is a characteristic of chronic mountain sickness (CMS). Currently, the pathogenesis of CMS remains unclear. This study was intended to investigate the role of EPAS1 in the proliferation of erythroblasts in CMS. Changes of HIF-1α and EPAS1/HIF-2α in the bone marrow erythroblasts of 21 patients with CMS and 14 control subjects residing at the same altitudes were determined by RT-qPCR and western blotting. We also developed a lentiviral vector, Lv-EPAS1/sh-EPAS1, to over-express/silence EPAS1 in K562 cells. Cells cycle and proliferation were detected by flow cytometry. Transcriptome analyses were carried out on Illumina. CMS patients showed a higher expression of EPAS1/HIF-2α in the bone marrow erythroblasts than those of controls. Variations in EPAS1 expression in CMS patients were positively correlated with RBC levels, and negatively correlated with SaO2. Over-expressing of EPAS1 in K562 cells accelerated the erythroid cells cycle progression and promoted the erythroid cells proliferation-and vice versa. Transcriptome data indicated that proliferation-related DEGs were significantly enriched in EPAS1 overexpression/silencing K562 cells. Our results suggest that EPAS1 might participate in the pathogenesis of EE by regulating the proliferation of erythroblasts.

Improved Molecular Packing of Self-Assembled Monolayer Charge Injectors for Perovskite Light-Emitting Diodes.

Self-assembled monolayers (SAMs) have shown great potential as hole injection materials for perovskite light-emitting diodes due to their low parasitic absorption and ability to adjust energy level alignment. However, the head and anchoring groups on SAM molecules with significant differences in polarity can lead to the formation of micelles in the commonly used alcoholic processing solvent, inhibiting the formation of an intact SAM. In this work, the introduction of methyl groups on carbazole in the phosphonic-acid-based SAM materials is found to facilitate energy level alignment and promote the formation of compact SAMs. The alternative molecular structure also enhances the solvent resistance of poly(9-vinylcarbazole), suppressing interfacial defect densities and nonradiative recombination processes in the emissive perovskites. PeLEDs based on the methyl-containing SAMs exhibit ∼30% enhancement in efficiency. These findings contribute to a better understanding of the design of SAM materials for PeLED applications.

[Effects of Rhodiola rosea on level of 5-hydroxytryptamine, cell proliferation and differentiation, and number of neuron in cerebral hippocampus of rats with depression induced by chronic mild stress].

OBJECTIVE: To explore the effects of Rhodiola rosea on the level of 5-hydroxytryptamine (5-HT), cell proliferation and differentiation, and number of neuron in cerebral hippocampus of rats with depression induced by chronic mild stress. METHOD: Fifty rats were divided into 5 groups: normal control, untreated, negative control, positive control and Rhodiola rosea-treated groups. There were 10 rats in each group. Except for normal control group, depression was induced in rats by chronic mild stress. The depressive rats in the other four groups were intragastrically administered with 0.5% sodium carboxymethycellulose, fluoxetine and Rhodiola rosea for 3 weeks. After the treatment, the content of 5-HT in the hippocampus was detected by high-performance liquid chromatography. The proliferating cells and differentiated cells in the hippocampus were labeled by bromodeoxyuridine (BrdU) or/and beta-tubulin III immunohistochemistry, and the number of hippocampal neurons was counted by morphometry. RESULT: Compared with the normal control group, the content of 5-HT, number of BrdU positive cells, percentage of BrdU and beta-tubulin III double labeled cells and number of neurons in cerebral hippocampus in the Rhodiola rosea-treated group were increased and recovered to normal level. CONCLUSION: Rhodiola rosea may enhance the level of 5-HT and promote the proliferation and differentiation of neural stem cells in the hippocampus of the depressive rats, and may play a role in saving injured neurons of the hippocampus.

[Effects of Valerian on the level of 5-hydroxytryptamine, cell proliferation and neurons in cerebral hippocampus of rats with depression induced by chronic mild stress].

OBJECTIVE: To explore the effects of Valerian on the level of 5-hydroxytryptamine (5-HT), cell proliferation and neuron number in cerebral hippocampus of rats with depression induced by chronic mild stress. METHODS: Seventy rats were divided into 7 groups: normal control, untreated, negative control, positive control, and low-, medium- and high-dose Valerian-treated groups. There were 10 rats in each group. Except for the normal control group, depression was induced in rats by chronic mild stress. The depressive rats in the other six groups were intragastrically administered with sodium carboxymethycellulose, fluoxetine, and low, medium and high-dose Valerian, respectively for 3 weeks. After the treatment, the proliferating cells in the hippocampus were labeled by injecting bromodeoxyuridine (BrdU) in 7 groups. The content of 5-hydroxytryptamine (5-HT) in the hippocampus was detected by high-performance liquid chromatography (HPLC), and the number of hippocampal neurons was counted by morphometry. RESULTS: Compared with the normal control group, the levels of 5-HT in the hippocampus in the low- and medium-dose Valerian-treated groups were increased and recovered to normal level. After the administration of low-dose Valerian for 3 weeks, the number of BrdU positive cells and neurons in the hippocampus of the depressive rats were recovered to the normal status. CONCLUSION: Minidose Valerian may promote the level of 5-HT and cell proliferation in the hippocampus of the depressive rats, and may play a role in saving injured neurons of the hippocampus.

[Effects of Rhodiola rosea on body weight and intake of sucrose and water in depressive rats induced by chronic mild stress].

OBJECTIVE: To explore the effects of Rhodiola rosea on the body weight and the intake of sucrose and water in depressive rats induced by chronic mild stress.dz METHODS: A total of 70 male SD rats were divided into seven groups, including normal control group (treated with 0.5% sodium carboxymethycellulose), untreated group, negative control group (treated with 0.5% sodium carboxymethycellulose), positive control group (treated with fluoxetine), low-, medium- and high-dose Rhodiola rosea group (treated with 1.5, 3, 6 g/kg Rhodiola rosea respectively). Except for rats in normal control group, the other sixty rats endured chronic stress for 4 weeks to establish the depression model. After that, rats were administered Rhodiola rosea for 3 weeks. During the whole experiment, the body weight, and sucrose intake, tap water intake of all rats were examined once a week. RESULTS: After the termination of the stress regime, compared with the normal control group, the body weight and 1% sucrose intake in depressive rats were decreased. After 3-week Rhodiola rosea treatment, the body weight and 1% sucrose intake increased in rats of the low-dose Rhodiola rosea group and recovered to the level of the normal control group. CONCLUSION: Low-dose Rhodiola rosea can increase the body weight and sucrose intake of depressive rats, making them recover to normal status.