Receptor for activated C kinase 1 (RACK1) has been shown to promote oral squamous cell carcinoma (OSCC) progression, and RACK1 expression levels have been negatively correlated with prognosis in patients with OSCC. Here, we investigated the impact of RACK1 OSCC expression on the recruitment and differentiation of tumor‐associated macrophages. High RACK1 expression in OSCC cells correlated with increased M2 macrophage infiltration in tumor samples from a clinical cohort study. Moreover, the combination of RACK1 expression and the M2/M1 ratio could successfully predict prognosis in OSCC. OSCC cells with high RACK1 expression inhibited the migration of THP‐1 cells, promoted M2‐like macrophage polarization in vitro, and increased the proportion of M2‐like macrophages in a xenograft mouse model. Moreover, both M1‐ and M2‐like macrophage polarization‐associated proteins were induced in macrophages cocultured with RACK1‐silenced cell supernatant. A mechanistic study revealed that the expression and secretion of C‐C motif chemokine 2 (CCL2), C‐C motif chemokine 5 (CCL5), interleukin‐6 (IL‐6), and interleukin‐1 (IL‐1) are closely related to RACK1 expression. In addition, blocking nuclear factor‐kappa B (NF‐κB) could promote M2‐like macrophage polarization. These results indicate that RACK1 and the M2/M1 ratio are predictors of a poor prognosis in OSCC. RACK1 promotes M2‐like polarization by regulating NF‐κB and could be used as a potential therapeutic target for antitumor immunity.
microRNAs (miRNAs) can be used as biomarkers for acute myocardial infarction (AMI). However, few reports have focused on the value of exosomal miRNAs in the mechanism of the pathophysiological process from stable coronary artery disease (SCAD) to AMI. Exosomes were isolated via ultracentrifugation after serum samples were collected. The exosomes were then identified by transmission electron microscopy, western blotting, and nanoparticle tracking analysis. The differential expression of miRNAs in exosomes from six AMI and six matching SCAD patients was screened using the Agilent Human miRNA Microarray Kit. Target genes of the candidate miRNAs were predicted via an online miRNA database, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Further validation was conducted through quantitative real‐time polymerase chain reaction with 60 exosome samples. The expression of 13 miRNAs was significantly downregulated in the AMI samples compared with the SCAD samples. In addition, we identified various target genes that are mainly involved in the pathways of cardiac rehabilitation and remodelling. Validation of the expression of candidate miRNAs indicated that exosomal miR‐1915‐3p, miR‐4,507, and miR‐3,656 were significantly less expressed in AMI samples than in SCAD samples, and area under the receiver‐operating‐characteristic curve (AUC) analysis showed that the expression of these miRNAs resulted in good predictive accuracy [miR‐1915‐3p (AUC: 0.772); miR‐4,507 (AUC: 0.684); and miR‐3,656 (AUC: 0.771)], suggesting that these serum exosomal miRNAs might be predictive for AMI at an early stage. Hence, exosomal miRNAs might play an important role in the pathophysiology of AMI and could serve as diagnostic biomarkers.
Paeoniflorin (PF), which is the main active ingredient in the root of Paeonia Radix, has many pharmacological effects. Here, we investigated the effect of PF on rat pulmonary artery smooth muscle cells (PASMCs) under hypoxic conditions and explored the mechanisms of the effects. The anti-proliferative effect of PF increased in a dose dependent manner. At the highest dose (20 μmol/L), the anti-proliferative effect of PF peaked at 24 h after administration. However, the selective A2B adenosine receptor (A2BAR) antagonist MRS1754 abolished it. PF increased A2BAR mRNA levels from 0.0763±0.0067 of β-actin mRNA levels (hypoxia group) to 0.1190±0.0139 (P<0.05) measured by Real Time Reverse Transcription-Polymerase Chain Reaction. A2BAR protein expression measured by Western Blot was also increased. PF inhibited the proliferation of PASMCs by blocking cell cycle progression in the S phase. These data indicated that activation of A2BAR might be involved in the anti-proliferative effect of PF on PASMCs under hypoxic conditions. The results suggested that a new mechanism of PF could be relevant to the management of clinical hypoxic pulmonary hypertension.
The clinical effectiveness of the erbium-doped yttrium-aluminum-garnet (Er:YAG) laser in patients with peri-implantitis remains unclear. The aim of this meta-analysis was to investigate the efficacy and safety of Er:YAG laser (ERL) compared to subgingival mechanical debridement (SMD) for the treatment of peri-implantitis. A systematic electronic literature search was conducted to identify randomized clinical trials (RCTs), followed by a manual search. Results were expressed as weighted mean differences (WMDs) with accompanying 95 % confidence intervals (CIs). The primary outcome measurements were changes in clinical attachment level (CAL) and probing depth (PD). Secondary outcome measurements included changes in gingival recession (GR). The meta-analysis was performed with fixed-effect or random-effect model according to the heterogeneity assessed by I (2) test. Visual asymmetry inspection of the funnel plot, Egger's regression test, and the trim-and-fill method were used to investigate publication bias. At 6 months, significant difference in PD reduction (p = 0.018) was observed for Er:YAG laser compared to SMD treatment, while no significant differences were detected in CAL gain and GR change; at 12 months, no significant difference was observed for any investigated outcome. The findings of this meta-analysis suggest that use of the Er:YAG laser as alternative to SMD could potentially provide short-time additional benefits, while there is no evidence of long-time superior effectiveness. As all included studies were not at low risk of bias, and only four studies were included in the meta-analysis, future long-term and well-designed RCTs reporting clinical and microbiological outcomes, considering the cost/effectiveness ratio, and having a high methodological quality are needed to clarify the effectiveness of Er:YAG laser.
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