Increased expression of miR-320b in blood plasma of patients in response to SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recent research has demonstrated how epigenetic mechanisms regulate the host-virus interactions in COVID-19. It has also shown that microRNAs (miRNAs) are one of the three fundamental mechanisms of the epigenetic regulation of gene expression and play an important role in viral infections. A pilot study published by our research group identified, through next-generation sequencing (NGS), that miR-4433b-5p, miR-320b, and miR-16-2-3p are differentially expressed between patients with COVID-19 and controls. Thus, the objectives of this study were to validate the expression of these miRNAs using quantitative real-time polymerase chain reaction (qRT-PCR) and to perform in silico analyses. Patients with COVID-19 (n = 90) and healthy volunteers (n = 40) were recruited. MiRNAs were extracted from plasma samples and validated using qRT-PCR. In addition, in silico analyses were performed using mirPath v.3 software. MiR-320b was the only miRNA upregulated in the case group com-pared to the control group. The in silico analyses indicated the role of miR-320b in the regulation of the KITLG gene and consequently in the inflammatory process. This study confirmed that miR-320b can distinguish patients with COVID-19 from control participants; however, further research is needed to determine whether this miRNA can be used as a target or a biomarker.

Pharmacokinetic Properties of Dapagliflozin in Hemodialysis and Peritoneal Dialysis Patients.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors attenuate incident cardiovascular outcomes, irrespective of baseline GFR, in conservatively managed CKD. As this condition inexorably progresses to demanding KRT, drug withdrawal is supported by the current lack of evidence of safety of SGLT2 inhibitors in dialysis. METHODS: This study was a prospective, single-center, open-label trial ( ClinicalTrials.gov identifier: NCT05343078 ) aimed at assessing the pharmacokinetic properties and safety of dapagliflozin in patients with kidney failure on regular dialysis regimens compared with those with type 2 diabetes and age- and sex-matched controls with normal kidney function. Peripheral blood samples were collected from both groups every 30 minutes for 4 hours and again after 48 hours after ingestion of dapagliflozin 10 mg, which occurred immediately before dialysis session initiation in the kidney failure group. This protocol occurred in drug-naïve patients and again after six daily doses of dapagliflozin to assess whether the drug had accumulated. The plasma and dialysate levels of dapagliflozin at each time point were determined by liquid chromatography and used to calculate pharmacokinetics parameters (peak concentration [C max ] and area under the plasma concentration-versus-time curve) for each participant. RESULTS: Dapagliflozin C max was 117 and 97.6 ng/ml in the kidney failure and control groups, respectively, whereas the corresponding accumulation ratios were 26.7% and 9.5%. No serious adverse events were reported for either group. Dapagliflozin recovered from dialysate corresponded to 0.10% of the administered dose. CONCLUSIONS: In patients with kidney failure on dialysis, dapagliflozin was well tolerated, was slightly dialyzable, and had nonaccumulating pharmacokinetic properties. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients (DARE-ESKD 1), NCT05343078.