Acute lung injury (ALI) is a frequent, but severe complication following sepsis in patients with critical illness. The present study aimed to investigate the potential role of microRNA-21 (miR-21) in the regulation of inflammation in the ALI induced by lipopolysaccharide (LPS) in vitro and in vivo. The levels of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-10, and the level of miR-21 expression were measured in the lungs of LPS-induced ALI rats and NR8383 alveolar macrophages (AMs). To confirm the regulatory effect of miR-21 in the inflammatory reactions of ALI, NR8383 cells were transfected with a mimic of miR-21 or an anti-miR-21 inhibitor, and the subsequent changes of the miR-21 level and the levels of inflammatory cytokines were detected. The underlying molecular mechanism was also investigated. LPS-induced ALI in rats resulted in significant overexpression of pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and miR-21, but reduced the expression of the anti-inflammatory cytokine IL-10. LPS treatment also led to a higher expression level of miR-21 and increased secretion of pro-inflammatory cytokines in NR8383 cells in a time-dependent manner. Manipulation with the miR-21 mimic significantly suppressed the LPS-mediated induction of TNF-α, IL-6 and IL-1β in NR8383 cells, while that induction was upregulated when miR-21 expression was silenced via transfection with the anti-miR-21 inhibitor. Further mechanism experiments revealed that miR-21 regulates LPS-induced inflammation responses via the Toll-like receptor 4 and nuclear factor-κB (Nf-κB) signaling pathway. miR-21 negatively regulates inflammatory responses in LPS-induced ALI by targeting the NF-κB signaling pathway, providing further insight into the molecular mechanism of ALI progression.
Propofol is a commonly used intravenous anesthetic. The aim of the study was to examine the mechanism of propofol in traumatic brain injury (TBI) by regulating interleukin (IL)-17 activity and maintaining the Th17/Treg balance. A rat model with moderate TBI was established using the weight-drop method. Rats with TBI were regularly injected with propofol and their brain injuries were monitored. The peripheral blood of rats was collected to measure the Th17/Treg ratio. MicroRNA (miR)-145-3p expression was detected in the brain tissues of rats and antagomiR-145-3p was injected into the lateral ventricles of their brains to verify the effect of miR-145-3p on brain injury. The downstream target of miR-145-3p was predicted. The targeting relationship between miR-145-3p and nuclear factor of activated T cells c2 (NFATc2) was confirmed. NFATc2 expression and phosphorylation of NF-κB pathway-related proteins were measured. Propofol alleviated brain injury in rats with TBI and maintained the Th17/Treg balance. Propofol upregulated miR-145-3p expression in rat brains, while the inhibition of miR-145-3p reversed the effect of propofol on brain injury. A binding relationship was observed between miR-145-3p and NFATc2. Furthermore, propofol decreased the phosphorylation of p65 and IκBα, and inhibited activation of the NF-κB pathway in the brains of rats with TBI. In conclusion, propofol maintained Th17/Treg balance and reduced inflammation in the rats with TBI via the miR-145-3p/NFATc2/NF-κB axis. cAN cUI 1
A colon tumor, one of the digestive tract malignant tumors, is harmful to human health. A potential new treatment still deserves attention. The development of a new drug needs more resources, including time and expense. Therefore, the old drug with new targets has become a current research hotspot. Fluvoxamine, as an antidepressant, could play an effect on inhibiting 5-hydroxytryptamine reuptake. In the present research, the antitumor effects and possible mechanisms of fluvoxamine are validated. The results showed that fluvoxamine significantly suppressed the migration and proliferation of tumor cells, and increased the apoptosis in vitro. Additionally, fluvoxamine significantly delays tumor development, and prompts the apoptosis in tumor tissues of mice-burdened colon tumors in vivo. The tumor suppression might be related with that fluvoxamine inhibits the expression of phosphorylated signal transducer and activator of transcription 3, matrix metalloproteinase 2, and cleaved-caspase 3. Importantly, fluvoxamine significantly reduces the expression level of programmed cell death ligand 1. This could be a possible reason that treatment with fluvoxamine drives the infiltration of T lymphocytes and M1-type macrophages in tumor tissues. Taken together, this research suggests that fluvoxamine might be a promising drug to treat colon cancer by inhibiting the proliferation and migration, inducing apoptosis, and even increasing the immune response of antitumor.
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