Expression Profiles of Dopamine-Related Genes and miRNAs Regulating Their Expression in Breast Cancer.

This study aimed to assess the expression profile of messenger RNA (mRNA) and microRNA (miRNA) related to the dopaminergic system in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A (n = 130), luminal B (n = 196, including HER2-, n = 100; HER2+, n = 96), HER2+ (n = 36), and TNBC (n = 43); they underwent surgery, during which tumor tissue was removed along with a margin of healthy tissue (control material). The molecular analysis included a microarray profile of mRNAs and miRNAs associated with the dopaminergic system, a real-time polymerase chain reaction preceded by reverse transcription for selected genes, and determinations of their concentration using enzyme-linked immunosorbent assay (ELISA). The conducted statistical analysis showed that five mRNAs statistically significantly differentiated breast cancer sections regardless of subtype compared to control samples; these were dopamine receptor 2 (DRD2), dopamine receptor 3 (DRD3), dopamine receptor 25 (DRD5), transforming growth factor beta 2 (TGF-ß-2), and caveolin 2 (CAV2). The predicted analysis showed that hsa-miR-141-3p can regulate the expression of DRD2 and TGF-ß-2, whereas hsa-miR-4441 is potentially engaged in the expression regulation of DRD3 and DRD5. In addition, the expression pattern of DRD5 mRNA can also be regulated by has-miR-16-5p. The overexpression of DRD2 and DRD3, with concomitant silencing of DRD5 expression, confirms the presence of dopaminergic abnormalities in breast cancer patients. Moreover, these abnormalities may be the result of miR-141-3P, miR-16-5p, and miR-4441 activity, regulating proliferation or metastasis.

Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A.

Studies indicate that mitogen-activated protein kinases (MAPKs) are activated and overexpressed in psoriatic lesions. The aim of the study was to assess changes in the expression pattern of genes encoding MAPKs and microRNA (miRNA) molecules potentially regulating their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes exposed to bacterial lipopolysaccharide A (LPS) and cyclosporine A (CsA). HaCaT cells were treated with 1 µg/mL LPS for 8 h, followed by treatment with 100 ng/mL cyclosporine A for 2, 8, or 24 h. Untreated cells served as controls. The molecular analysis consists of microarray, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay analyses. The statistical analysis of the obtained results was performed using Transcriptome Analysis Console and STATISTICA 13.5 PL with the statistical significance threshold of p < 0.05. Changes in the expression profile of six mRNAs: dual-specificity phosphatase 1 (DUSP1), dual-specificity phosphatase 4 (DUSP4), mitogen-activated protein kinase kinase 2 (MAP2K2), mitogen-activated protein kinase kinase 7 (MAP2K7), mitogen-activated protein kinase kinase kinase 2 (MAP3K2) and mitogen-activated protein kinase 9 (MAPK9) in cell culture exposed to LPS or LPS and the drug compared to the control. We observed that under the LPS and cyclosporine treatment, the expression o/ miR-34a, miR-1275, miR-3188, and miR-382 changed significantly (p < 0.05). We demonstrated a potential relationship between DUSP1 and miR-34a; DUSP4 and miR-34a, miR-382, and miR-3188; MAPK9 and miR-1275, MAP2K7 and mir-200-5p; MAP3K2 and mir-200-5p, which may be the subject of further research in the context of psoriasis.

The Adequacy of Anesthesia Guidance for Vitreoretinal Surgeries with Preemptive Paracetamol/Metamizole.

Despite the possibility of postoperative pain occurrence, in some patients, vitreoretinal surgeries (VRSs) require performance of general anesthesia (GA). The administration of intraoperative intravenous rescue opioid analgesics (IROA) during GA constitutes a risk of perioperative adverse events. The Adequacy of Anesthesia (AoA) concept consists of an entropy electroencephalogram to guide the depth of GA and surgical pleth index (SPI) to optimize the titration of IROA. Preemptive analgesia (PA) using cyclooxygenase-3 (COX-3) inhibitors is added to GA to minimize the demand for IROA and reduce postoperative pain. The current analysis evaluated the advantage of PA using COX-3 inhibitors added to GA with AoA-guided administration of IROA on the rate of postoperative pain and hemodynamic stability in patients undergoing VRS. A total of 165 patients undergoing VRS were randomly allocated to receive either GA with AoA-guided IROA administration with intravenous paracetamol/metamizole or with preemptive paracetamol or metamizole. Preemptive paracetamol resulted in a reduction in the IROA requirement; both preemptive metamizole/paracetamol resulted in a reduced rate of postoperative pain as compared to metamizole alone. We recommend using intraoperative AOA-guided IROA administration during VRS to ensure hemodynamic stability alongside PA using both paracetamol/metamizole to reduce postoperative pain.

Postoperative Nausea and Vomiting following Endoscopic Sinus Surgery under the Guidance of Adequacy of Anesthesia or Pupillometry with Intravenous Propofol/Remifentanil.

Postoperative nausea and vomiting (PONV) constitutes an adverse event after endoscopic sinus surgery (ESS) under general anesthesia (GA) with intravenous opioids, such as remifentanil (RMF). Monitoring the nociception/antinociception balance using the surgical pleth index (SPI) or pupillary dilatation reflex (PRD) helps guide intravenous RMF infusion. We aimed to investigate whether their employment could help reduce the incidence of PONV in patients undergoing ESS. The data of 30 patients from the GA group, 31 from the SPI group, and 28 from the PRD group were analyzed. The initial RMF infusion rate of 0.25 µg/kg body weight/minute was increased by 50% when the SPI, PRD, or Boezaart Bleeding Scale (BBS) were elevated by >15, >5%, or >2 points, respectively, until they normalized. PONV was present in 7/89 patients (7.9%): 2/31 patients (6.5%) of the SPI group, 1/30 patients (3.3%) of the GA group, and 4/28 patients (14.3%) of the PRD group. Neither PRD nor SPI guidance for RMF administration reduced the incidence of PONV compared to standard practice. Further studies are required in order to investigate the possibility of PONV eradication in patients undergoing ESS under GA when it is possibly combined with paracetamol/metamizole preventive analgesia, as well as those using antiemetic prophylaxis based on the Apfel Score and premedication with midazolam.