Acute kidney injury (AKI) is a disease that is characterized by a rapid decline in renal function and has a relatively high incidence in hospitalized patients. Sepsis, renal hypoperfusion, and nephrotoxic drug exposure are the main causes of AKI. The major therapy measures currently include supportive treatment, symptomatic treatment, and kidney transplantation. These methods are supportive treatments, and their results are not satisfactory. Fortunately, many new treatments that markedly improve the AKI therapy efficiency are emerging. These include antioxidant therapy, ferroptosis therapy, anti-inflammatory therapy, autophagy therapy, and antiapoptotic therapy. In addition, the development of nanotechnology has further promoted therapeutic effects on AKI. In this review, we highlight recent advances in the development of nanocarriers for AKI drug delivery. Emphasis has been placed on the latest developments in nanocarrier modification and design. We also summarize the applications of different nanocarriers in AKI treatment. Finally, the advantages and challenges of nanocarrier applications in AKI are summarized, and several nanomedicines that have been approved for clinical trials to treat diverse kidney diseases are listed.

Previous studies have identified critical roles of IL-27 in the pathological mechanisms of sepsis, and blockade of IL-27 may be a promising alternative therapy for sepsis. The purpose of this study was to evaluate the clinical relevance of IL-27 genetic polymorphisms in sepsis and to further characterize their effect on IL-27 expression and inflammatory processes following sepsis. A total of 885 septic patients and 1101 healthy controls were enrolled and genotyped for IL-27 genetic variants (rs153109/−964A > G and rs17855750/2905 T > G). Quantitative real-time PCR and enzyme-linked immunosorbent assays were performed to detect IL-27 expression and cytokine production. The effect of the rs153109 polymorphism on IL-27 promoter activity was evaluated using a luciferase reporter assay, and THP-1 cell apoptosis was calculated using an annexin V apoptosis assay. No significant differences in the genotype/allele frequencies were observed between patients with sepsis and healthy controls, suggesting that these two IL-27 polymorphisms may not influence susceptibility to sepsis. The -964AA genotype was overrepresented in patients with severe sepsis/septic shock relative to patients with the sepsis subtype, and the A allele was significantly associated with 28-mortality in sepsis. Patients carrying the -964AA genotype exhibited significantly higher expression levels of IL-27 than the GA/GG genotype carriers. The results of an in vitro (lipopolysaccharide (LPS))-stimulated experiment showed that this sepsis-associated high-risk AA genotype significantly increased IL-27 levels and enhanced TNF-α and IL-1β production in the peripheral blood mononuclear cells (PBMCs) upon exposure to LPS in vitro. Furthermore, luciferase reporter assays indicated that the high-risk -964A allele resulted in increased promoter activities compared to the non-risk allele in THP-1 and 293 T cells. Additionally, IL-27 treatment significantly enhanced TNF-α and IL-6 secretion and apoptosis of THP-1 cells upon LPS stimulation. These results provided evidence that the IL-27 -964A > G polymorphism functionally enhanced IL-27 expression and promoted sepsis-induced inflammatory responses, which ultimately resulted in promoting the progression of sepsis and poor prognosis.

Background. Previous studies have demonstrated pivotal roles of disintegrin and metalloproteinase 10 (ADAM10) in the pathogenesis of sepsis. MicroRNA- (miR-) 23b has emerged as an anti-inflammatory factor that prevents multiple autoimmune diseases. However, the underlying mechanisms of miR-23b in the regulation of ADAM10 and sepsis remain uncharacterized. Methods. The expression levels of ADAM10 and miR-23b were detected by quantitative RT-PCR and western blot analysis. Cytokine production and THP-1 cell apoptosis were measured by enzyme-linked immunosorbent and annexin V apoptosis assays. Bioinformatics analyses and qRT-PCR, western blot, and luciferase reporter assays were performed to identify ADAM10 as the target gene of miR-23b. Results. miR-23b expression was downregulated in the peripheral blood mononuclear cells of sepsis patients and LPS-induced THP-1 cells and was negatively correlated with the expression of ADAM10 and inflammatory cytokines. miR-23b regulated ADAM10 expression by directly binding to the 3′-UTR of ADAM10 mRNA. The overexpression of miR-23b alleviated the LPS-stimulated production of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and apoptosis by targeting ADAM10 in THP-1 cells. The inhibitor or knockdown of ADAM10 elicited effects similar to those of miR-23b on THP-1 cells upon LPS stimulation. Conclusions. The present study demonstrated that miR-23b negatively regulated LPS-induced inflammatory responses by targeting ADAM10. The molecular regulatory mechanism of miR-23b in ADAM10 expression and sepsis-induced inflammatory consequences may provide potential therapeutic targets for sepsis.

Nafamostat mesilate (NM), a broad-spectrum and potent serine protease inhibitor, can be used as an anticoagulant during extracorporeal circulation, as well as a promising drug effective against cor...

Previous studies demonstrated significant roles of autophagy in the pathogenesis of sepsis, but few studies focused on the effect of autophagy-related SNPs on sepsis susceptibility. In this present study, five polymorphisms of ATG5/ATG16L1 were investigated for the possible risk on sepsis in a Chinese Han population. Our results showed that ATG5 expression levels decreased with the severity of sepsis, and rs506027 T > C and rs510432 G > A were associated with sepsis progression and mortality. Moreover, the rs506027 TT and rs510432 GG carriers also exhibited increased expression levels of ATG5. Functional assays showed that ATG5 knockdown elevated the secretion of pro-inflammatory cytokines in THP-1 cells, and the extracted mononuclear cell of the risk C-A carriers exhibited decreased ATG5 expression levels, leading to enhanced releases of TNF-α and IL-1β under LPS stimulation in vitro. Furthermore, ATG5 T-G haplotype mutation showed higher promoter activities compared to C-A haplotype mutation, suggesting the effect of these SNPs on ATG5 gene transcription. Taken together, these results above indicated that these two ATG5 promoter polymorphisms may be functional and clinically significant for sepsis progression, underscoring its potentially therapeutic implications for sepsis and other inflammatory diseases.

Sepsis, an inflammation-related clinical syndrome, is characterized by disrupted immune homeostasis accompanied by infection and multiple organ dysfunction as determined by the Sequential Organ Failure Assessment (SOFA). Substantial evidence has recently suggested that lncRNAs orchestrate various biological processes in diseases, and lncRNAs play special roles in the diagnosis and management of sepsis. To date, very few reviews have provided clear and comprehensive clues to demonstrate the roles of lncRNAs in the pathogenesis of sepsis. Based on previously published studies, in this review, we summarize the different functions of lncRNAs in sepsis-induced cellular disorders and sepsis-induced organ failure to show the potential roles of lncRNAs in the diagnosis and management of sepsis. We further depict the function of some lncRNAs known to be pivotal regulators in the pathogenesis of sepsis to discuss the underlying molecular events. Additionally, we list and discuss several hotspots in research on lncRNAs, which may be conducive to future lncRNA-targeted therapeutic approaches for sepsis treatment.