The gut-lung axis in critical illness: microbiome composition as a predictor of mortality at day 28 in mechanically ventilated patients.

Background: Microbial communities are of critical importance in the human host. The lung and gut microbial communities represent the most essential microbiota within the human body, collectively referred to as the gut-lung axis. However, the differentiation between these communities and their influence on clinical outcomes in critically ill patients remains uncertain.

AGEs induce high expression of Dll4 via endoplasmic reticulum stress PERK signaling-mediated internal ribosomal entry site mechanism in macrophages.

Background And Aim: Advanced glycation end products (AGEs)- exposed macrophages was characterized by Delta-like ligand 4 (Dll4) high expressed and has been shown to participate in diabetes-related atherosclerosis. This study was aimed to investigate the translational regulatory mechanism of Dll4 high expression in macrophages exposed to AGEs.

Methods: Human Dll4 5' untranslated region (5'UTR) sequence was cloned and inserted into a bicistronic reporter plasmid.

Nrp-1 Mediated Plasmatic Ago2 Binding miR-21a-3p Internalization: A Novel Mechanism for miR-21a-3p Accumulation in Renal Tubular Epithelial Cells during Sepsis.

The mechanism underlying sepsis-associated acute kidney injury (SAKI), which is an independent risk factor for sepsis-associated death, is unclear. A previous study indicates that during sepsis miR-21a-3p accumulates in renal tubular epithelial cells (TECs) as the mediator of inflammation and mediates TEC malfunction by manipulating its metabolism. However, the specific mechanism responsible for the accumulation of miR-21a-3p in TECs during sepsis is unrevealed.

MiR-21-3p Plays a Crucial Role in Metabolism Alteration of Renal Tubular Epithelial Cells during Sepsis Associated Acute Kidney Injury via AKT/CDK2-FOXO1 Pathway.

Objective: Sepsis and associated acute kidney injury (SAKI) are determined to be closely related to poor prognosis. Because the metabolic alterations of tubular epithelial cells (TECs) are crucial for the occurrence and development of SAKI, we carried out this present study to identify the metabolism changes of TECs during SAKI and relevant mechanisms.

Methods: Rat SAKI model and rat tubular epithelial cell line were used in our study.

IQGAP1 mediates podocyte injury in diabetic kidney disease by regulating nephrin endocytosis.

Diabetic kidney disease (DKD) is a complication associated with diabetes and is a major public health problem in modern society. Podocyte injury is the central target of the development of DKD, and the loss or dysregulation of nephrin, a key structural and signalling molecule located in the podocyte slit diaphragm (SD), initiates potentially catastrophic downstream events within podocytes. IQGAP1, a scaffold protein containing multiple protein-binding domains that regulates endocytosis, can interact with nephrin in podocytes.

Novel ASK1 inhibitor AGI-1067 improves AGE-induced cardiac dysfunction by inhibiting MKKs/p38 MAPK and NF-κB apoptotic signaling.

Heart failure has been identified as one of the clinical manifestations of diabetic cardiovascular complications. Excessive myocardium apoptosis characterizes cardiac dysfunctions, which are correlated with an increased level of advanced glycation end products (AGEs). In this study, we investigated the participation of reactive oxygen species (ROS) and the involvements of apoptosis signal-regulating kinase 1 (ASK1)/mitogen-activated protein kinase (MAPK) kinases (MKKs)/p38 MAPK and nuclear factor κB (NF-κB) pathways in AGE-induced apoptosis-mediated cardiac dysfunctions.

Lipopolysaccharide Mediates the Destruction of Intercellular Tight Junction among Renal Tubular Epithelial Cells via RhoT1/SMAD-4/JAM-3 Pathway.

The morbidity of sepsis induced acute kidney injury remains unacceptable high and the mechanisms of that disease remains unclear. For urine backleak and intercellular tight junction among tubular epithelial cells (TECs) destruction often occur during sepsis induced acute kidney injury, we examined whether lipopolysaccharide could damage intercellular tight junction among TECs and associated mechanisms in our present study. HK-2 cells were cultured, transfected with different SiRNAs and stimulated with LPS and PYR-41.

Blood purification treatment initiated at the time of sepsis diagnosis effectively attenuates serum HMGB1 upregulation and improves patient prognosis.

The aim of the present study was to investigate the increase in serum and urine levels of high mobility group box protein 1 (HMGB1) during sepsis and the effect of blood purification treatments on HMGB1 levels and patient prognosis. A total of 40 intensive care patients with sepsis were randomly assigned to different groups (n=10 per group): A control group (sepsis group), a continuous renal replacement treatment (CRRT) group, a hemoperfusion (HP) group and an HP+CRRT group. The blood purification treatments using HP and/or CRRT were performed immediately after the diagnosis of sepsis.

HMGB1 Turns Renal Tubular Epithelial Cells into Inflammatory Promoters by Interacting with TLR4 During Sepsis.

Our study was undertaken to investigate whether the inflammatory mediator high-mobility group box 1 (HMGB1) can enter the renal tissue and urine and what is the functional change of renal tubular epithelial cells (TECs) interacting with HMGB1 during sepsis. We found that the transcription levels of interleukin 1 (IL-1) and interleukin 6 (IL-6) mRNA in TECs increased significantly during sepsis and these processes can be blocked by splenectomy. We also found out HMGB1 accumulated in the renal tissue and entered urine during sepsis and toll-like receptor 4 (TLR4) was expressed by TECs.