Hestervittrup0218

Moreover, minocycline significantly and dose-dependently promoted regulatory macrophage polarization but decreased pro-inflammatory macrophage polarization. Furthermore, mechanism studies showed that TAK1 and its downstream pathway p38/JNK/ERK1/2/p65 were inhibited by minocycline, which led to lower IL-1β and TNFα expression, but increased IL-10 expression.

Altogether, these results suggest that minocycline is highly effective against peripheral nerve adhesion through anti-fibrosis, anti-inflammation, and myelination protection, making it a highly promising candidate for treating adhesion-related disorders.

Altogether, these results suggest that minocycline is highly effective against peripheral nerve adhesion through anti-fibrosis, anti-inflammation, and myelination protection, making it a highly promising candidate for treating adhesion-related disorders.

Empagliflozin (EMPA) reduces heart failure hospitalization and mortality. The benefit in terms of ventricular arrhythmia and contractility has not been explored.

To determine the direct effects of EMPA on ventricular arrhythmia and cardiac contractility in an ex-vivo model of global ischemia-reperfusion (I/R).

Langendorff-perfused rabbit hearts were subjected to 30min of complete perfusion arrest and reperfusion. Either EMPA (1μM) or normal saline (controls) was then infused into the perfusate in a randomized fashion. Ten minutes following drug infusion, calcium imaging was performed. At the end of each experiment, the heart was electrically stimulated 5 times to assess the inducibility of ventricular fibrillation (VF). In a separate series of experiments, left ventricular (LV) pressure and epicardial NADH fluorescence were simultaneously recorded. LV specimens were then collected for western blotting.

Post-ischemia, EMPA treatment was associated with reduction in the induction of VF >10s (rate of induction 16.7±3.3% vs. 60±8.7% in control hearts, p=0.003), improvement of LV developed pressure (LVDP; 68.10±9.02% vs. 47.61±5.15% in controls, p=0.03) and reduction of NADH fluorescence (87.42±2.79% vs. 112.88±2.27% in control hearts, p=0.04) along with an increase in NAD+/NADH ratio (2.75±0.55 vs. 1.09±0.32 in the control group, p=0.04) A higher calcium amplitude alternans threshold was also observed with EMPA-treatment (5.42±0.1Hz vs. 4.75±0.1Hz in controls, p=0.006). Sodium-glucose co-transporter-2 (SGLT2) expression was not detected in LV tissues.

EMPA treatment reduced ventricular arrhythmia vulnerability and mitigated contractile dysfunction in the global I/R model while improving calcium cycling and mitochondrial redox by SGLT2-independent mechanisms.

EMPA treatment reduced ventricular arrhythmia vulnerability and mitigated contractile dysfunction in the global I/R model while improving calcium cycling and mitochondrial redox by SGLT2-independent mechanisms.

MicroRNAs are well-established players in post-transcriptional gene modulation. We aim to explore the role of microRNA-15a-5p (miR-15a-5p)/sex determining region Y-box 9 (Sox9)/nuclear factor-κB (NF-κB) axis in inflammation and apoptosis of murine nucleus pulposus cells (NPCs) in intervertebral disc degeneration (IVDD).

Expression levels of miR-15a-5p and Sox9 in disc tissues from IVDD patients were determined. The IVDD mouse models were established by disc puncture, and the modeled mice were accordingly injected with miR-15a-5p antagomir and/or overexpressed Sox9 plasmid, or their negative controls. Then, the expression of miR-15a-5p, Sox9 and p-p65, pathological changes and the apoptosis of NPCs in IVDD mouse intervertebral disc tissues were measured. The NPCs were isolated and cultured, which were then transfected with miR-15a-5p inhibitor, overexpressed or silenced Sox9 plasmids, or the NCs. Next, the expression of miR-15a-5p and Sox9, apoptosis, proliferation and cell cycle distribution of NPCs, and the contents of inflammatory factors in the NPCs were evaluated.

MiR-15a-5p expression was increased while Sox9 expression was reduced in intervertebral disc tissues from IVDD patients and mice. Mouse NPCs were successfully isolated. The down-regulated miR-15a-5p could elevate Sox9 to activate p-p65 expression, suppress NPC apoptosis and inflammatory factor contents, promote proliferation of NPCs, and arrest the NPCs at S and G2/M phases. However, these effects could be reversed by silencing Sox9.

Reduction of miR-15a-5p elevated Sox9 to inhibit the inflammatory response and apoptosis of NPCs in IVDD mice through the NF-κB pathway. This study may be helpful for IVDD treatment.

Reduction of miR-15a-5p elevated Sox9 to inhibit the inflammatory response and apoptosis of NPCs in IVDD mice through the NF-κB pathway. This study may be helpful for IVDD treatment.

Exosomal transfer of miRNAs affects recipient cell proliferation and chemoresistance. Tamoxifen solubility dmso Here, we aimed to investigate the role of exosomal miRNAs in controlling cisplatin resistance in non-small cell lung carcinoma (NSCLC).

Paired tumor and normal tissue-derived exosomes were collected from NSCLC patients with low or high responsiveness to cisplatin treatment. The results showed that the microRNA-4443 (miR-4443) level was upregulated in cisplatin-resistant NSCLC tumor tissue-derived exosomes compared with cisplatin-sensitive tissue-derived exosomes. Cisplatin-resistant cells (A549-R) were generated from the parental cells (A549-S). Resistant exosomes conferred cisplatin resistance by transferring miR-4443 to sensitive cells. Moreover, overexpression of miR-4443 inhibited FSP1-mediated ferroptosis induced by cisplatin treatment in vitro and enhanced tumor growth in vivo.

Through bioinformatics analysis and luciferase assays, METTL3 was confirmed as a direct target gene of miR-4443. Further mechanistic analysis showed that miR-4443 regulated the expression of FSP1 in an m6A manner via METLL3.

Our findings provide more in-depth insight into the chemoresistance of NSCLC and support the therapeutic potential of targeting ferroptosis.

Our findings provide more in-depth insight into the chemoresistance of NSCLC and support the therapeutic potential of targeting ferroptosis.