The role of RNA methylation on the sixth N atom of adenylate (m⁶A) in acute kidney injury (AKI) is unknown. FTO (fat mass and obesity-associated protein) reverses the m⁶A modification in cisplatin-induced AKI. Here, we aimed to determine FTO's role in AKI. We induced AKI in c57BL/6 mice by intraperitoneal cisplatin injection and treated the animal with vehicle or an FTO inhibitor meclofenamic acid (MA) for 3 days. Moreover, as an in vitro model, human kidney proximal tubular cells (HK2 cells) were treated with cisplatin. We found that the cisplatin treatment reduces FTO expression and increases m⁶A levels in vivo and in vitro. MA aggravated renal damage and increased apoptosis in cisplatin-treated kidneys, phenotypes that were correlated with reduced FTO expression and increased m⁶A levels. Moreover, MA promoted apoptosis in cisplatin-treated HK2 cells, which was correlated with the reduced FTO expression and increased m⁶A in HK2 cells. FTO protein overexpression reduced m⁶A levels and inhibited apoptosis in cisplatin-treated HK2 cells and also blocked the MA-induced increase in m⁶A levels and apoptosis rates. In agreement, overexpression of the m⁶A-generating methyltransferase-like 3 and 14 (METTL3 and METTL14) or siRNA-mediated FTO knockdown promoted apoptosis and enhanced m⁶A levels in cisplatin-treated HK2 cells. MA increased p53 mRNA and protein levels in AKI both in vitro and in vivo, and FTO overexpression reduced p53 expression and reversed the MA-induced p53 increase in AKI. In conclusion, reduced renal FTO expression in cisplatin-induced AKI increases RNA m⁶A levels and aggravates renal damages.

Overwhelming activation of granulocytes and monocytes is central to inflammatory responses during sepsis. Granulocyte and monocyte adsorptive apheresis (GMA) is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads and selectively adsorbs granulocytes and monocytes from the peripheral blood. In this study, septic rats received the GMA treatment for 2 h at 18 h after cecal ligation and puncture. GMA selectively adsorbed activated neutrophils and monocytes from the peripheral blood, reduced serum inflammatory cytokine expression, and seemed to improve organ injuries and animal survival. GMA potentially reduced lung injury by alleviating the infiltration of inflammatory cells and the secretion of cytokines. This study showed that selective granulocyte and monocyte adsorption with cellulose acetate beads might ameliorate cecal ligation and puncture (CLP)-induced sepsis and improve survival and organ function.

Multiple myeloma is a primary malignancy of bone marrow characterized by the clonal proliferation of plasma cells and production of monoclonal immunoglobulin. The disease occurs more frequently in males, with the average age at diagnosis being ~60 years. The first manifestation of multiple myeloma is varied and depends on the sites and extent of involvement. The predominant clinical symptoms of multiple myeloma are associated with bone pain and renal dysfunction. Neoplastic cells usually produce large amounts of monoclonal immunoglobulin light or heavy chains that can be detected in serum or urine, while plasmacytoma may be identified on marrow biopsy. The present study reported on the case of a 69‑year‑old male patient presenting with a complaint of a painful lesion in the left maxilla. Physical examination, imaging, laboratory investigations and biopsy were conducted, confirming the diagnosis of multiple myeloma. The results obtained suggest that the dentist should address oral manifestations as first indications of multiple myeloma.

Background: Acute kidney injury (AKI) is a clinical syndrome characterized by significant morbidity and a high death rate. Interleukin (IL)-27 is a newly described member of the IL-6/IL-12 heterodimeric cytokine family and displays anti-inflammatory and antiapoptotic properties. Objectives: To determine the effect and mechanism of IL-27 in AKI. Method: We used a mouse model of renal ischemia/reperfusion (I/R) injury to investigate whether IL-27 has a therapeutic potential for the treatment of AKI. For the IL-27 administration group, IL-27 protein was injected 1 h before ischemia. Human proximal tubular epithelial cells were exposed to ischemia for 2 h and followed by 2 h of reperfusion (I2h+R2h treatment) used as an in vitro model to investigate the effect of IL-27. Results: Two IL-27 subunits, Epstein-Barr virus gene 3 and p28, were upregulated in kidneys 24 h after I/R. Renal expression of IL-27 receptor subunits (gp130 and WSX-1) was also increased. Treatment with IL-27 reduced structural/functional damages, ameliorated renal inflammation, inhibited the cleaved caspase-3 expression, upregulated antiapoptotic protein Bcl-2 and downregulated proapoptotic protein Bax in the kidneys of mice subjected to I/R. Meanwhile, the level of IL-27 receptor on renal tubular epithelial cells was increased after I2h+R2h treatment, and IL-27 administration suppressed I2h+R2h-induced epithelial cell apoptosis. Furthermore, IL-27 treatment led to activation of signal transducer and activator of transcription 3 (STAT3) both in vivo and in vitro, and IL-27-mediated protection against I2h+R2h injury was abolished by STAT3 inhibition. Conclusions: IL-27 protects against renal I/R injury by activating STAT3, suggesting that IL-27 may represent a novel strategy for the treatment of AKI.

Frailty is common among individuals with chronic kidney disease (CKD), whereas its impact on incident CKD risk remains unknown. This study aimed to prospectively evaluate the association between frailty and incident CKD risk, exploring the potential modification role of genetic risk factors (GRS). A cohort of 275,442 UK Biobank participants (mean age 55.3 ± 8.1 years, 43.4% male) without CKD were included. Physical frailty was defined by Fried Frailty phenotypes (FP) and Rockwood Frailty Index (FI). New-onset CKD was identified through hospital inpatient records and death register. GRS for CKD were calculated based on 27 single-nucleotide variants. Cox proportional hazards models and Fine-Gray competing risk models were applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 14.1 years, 5771 incident CKD cases were documented. Cox models indicated that prefrailty and frailty were associated with an increased CKD risk, with HRs (95% CI) of 1.17 (1.10–1.24) and 1.74 (1.58–1.91) for FP, and 1.33 (1.24–1.41) and 1.87 (1.72–2.04) for FI. These associations remained significant after adjusting for competing risks. Estimated population attributable fractions of frailty for CKD were 5.6% (FP) and 9.9% (FI). A positive non-linear relationship between FI and CKD incidence was observed in women (P non-linearity < 0.001). Associations were strengthened in women and those under 60 years of age (P for interaction < 0.05). Frailty significantly interacted with genetic susceptibility (P for interaction < 0.001), with the highest CKD risk observed in participants with high genetic risk and frailty (HR, 95% CI; FI: 2.28, 1.90–2.74; FP: 1.88, 1.52–2.33). Pre-frailty and frailty associated with incident CKD, with further modulation by GRS. These findings have important implications of frailty assessment and management in CKD prevention.