The Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway is a principal signaling pathway for the signal transduction of many pivotal cytokines involved in sepsis. Binding of cytokines to corresponding receptors can activate associated JAK kinases, which selectively phosphorylate STATs. Activated STATs then translocate to the nucleus and play a critical role in the transcription of target genes. During the past several years, significant progress has been made in the understanding of the roles of JAK/STAT pathway in sepsis. The aims of this review are to describe the present knowledge about JAK/STAT signaling pathway, describe the specific roles of JAK/STAT pathway in sepsis, and put forward the prospect for future studies of JAK/STAT signaling pathway in sepsis. A PubMed database search was performed for studies of JAKs and STATs in sepsis. It has been shown that a variety of cytokines can exert their biological effects via the JAK/STAT signaling pathway. JAK/STAT pathway has been shown related to the release of various cytokines and inflammatory mediators and involved in the regulation of immune response in sepsis. Moreover, JAK/STAT pathway has been shown involved in organ damage and other dysfunctions in sepsis models.

Citrulline (Cit) supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg) concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP) model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1β were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

Background Long noncoding RNAs (lncRNAs) are involved in physiological and pathological processes. However, no studies have been conducted on the relationship between lncRNAs and renal aging. Results First, we evaluated the histopathology of young (3-month-old) and old (24-month-old) C57BL/6J mouse kidneys. Masson trichrome staining and PAS staining showed interstitial collagen deposition and fibrosis, mesangial matrix expansion, a thicker basement membrane and renal interstitial fibrosis in old mouse kidneys. Senescence-associated β-galactosidase (SA-β-gal)-positive areas in the kidneys of old mice were significantly elevated compared to those of young mice. Then, we analyzed the differential expression of lncRNAs and mRNAs in the kidneys of young and old mouse kidneys by RNA-seq analysis. 42 known and 179 novel differentially expressed lncRNAs and 702 differential mRNAs were detected in the mouse kidney. Next, we focused on the differentially expressed mRNAs and lncRNAs by RNA-seq. GO and KEGG analyses were performed based on differentially expressed mRNAs between young and old mouse kidneys. Transregulation based on RIsearch and the correlation coefficient of mRNA-lncRNA were also calculated. The mRNA-lncRNA network was constructed by choosing a Spearman correlation coefficient > 0.9 or <-0.9. GO and KEGG pathway enrichment analyses revealed that differentially expressed mRNAs participated in aging-related pathways. A total of 10 lncRNAs and trans-regulated mRNAs were constructed. Finally, we validated the role of lncRNA Gm43360 by CCK-8, flow cytometry, western blot and SA-β-gal staining. The expression level of Adra1a was positively correlated and Csnk1a1 was negatively correlated with lncRNA Gm43360. The cell counting kit-8 (CCK-8) results showed that lncRNA Gm43360 promoted cell viability. LncRNA Gm43360 increased the percentage of S phase cells and decreased the percentage of G1 phase cells compared with the negative control. LncRNA Gm43360 decreased the expression of p53, p21 and SA-β-gal. Conclusions LncRNA Gm43360 may play a protective role in kidney aging.