• biomarker
• kidney
• normothermic machine perfusion
• pig
• reperfusion-injury

• Animals
• Kidney/metabolism
• Kidney/pathology
• Swine
• Perfusion/methods
• Biomarkers
• Organ Preservation/methods
• Kidney Transplantation

• 100382963 European Regional Development Fund

• 3D renal proximal tubule
• Hyperinflammation
• In vitro renal toxicity model
• Peripheral blood mononuclear cells

• Humans
• Coculture Techniques
• Leukocytes, Mononuclear
• Cell Line
• Lipopolysaccharides
• Inflammation

• 1711195891 Korea Institute of Toxicology
• Global-22-011 National Research Council of Science and Technology

• Homer2
• IQCH
• LCN2
• NGAL
• exome sequencing
• operational tolerance
• primary cilium
• renal transplantation

Osteoarthritis (OA) is the most common joint disease that can cause pain and disability in adults. The main pathological characteristic of OA is cartilage degeneration, which is caused by chondrocyte apoptosis, cartilage matrix degradation, and inflammatory factor destruction. The current treatment for patients with OA focuses on delaying its progression, such as oral anti-inflammatory analgesics or injection of sodium gluconate into the joint cavity. Primary cilia are an important structure involved in cellular signal transduction. Thus, they are very sensitive to mechanical and physicochemical stimuli. It is reported that the primary cilia may play an important role in the development of OA. Here, we review the correlation between the morphology (location, length, incidence, and orientation) of chondrocyte primary cilia and OA and summarize the relevant signaling pathways in chondrocytes that could regulate the OA process through primary cilia, including Hedgehog, Wnt, and inflammation-related signaling pathways. These data provide new ideas for OA treatment.

The effect of hemodialysis combined with MDT intervention on the degree of renal fibrosis and renal function in uremia patients was studied. 118 patients with uremia admitted to the hospital were selected as the research object, and they were divided into two groups according to the random number table method, 59 cases in the control group and 59 cases in the experimental group. The control group was treated with hemodialysis, and the experimental group was treated with MDT multimode intervention on the basis of hemodialysis. The differences in renal fibrosis, renal function, and satisfaction after treatment were compared before treatment and at 1, 3, and 6 months after treatment. The experimental results showed that hemodialysis combined with MDT multimode intervention in uremia patients could reduce renal fibrosis and improve renal function and improve clinical satisfaction evaluation.

Polycystic kidney disease (PKD) is one of the most common inherited diseases and is characterized by the development of fluid-filled cysts along multiple segments of the nephron. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD, which is caused by mutations in either PKD1 or PKD2 genes that encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. As ADPKD progresses, cysts enlarge and disrupt normal kidney architecture, eventually leading to kidney failure. Our previous study showed that overexpression of exogenous kidney-specific neutrophil gelatinase-associated lipocalin (NGAL) reduced cyst progression and prolonged the lifespan of ADPKD mice (Pkd1^L3/L3, 2L3 for short). In this study, we attempted to explore the underlying mechanism of reduced cyst progression in the presence of NGAL using immortalized 2L3 cells. The results of MTT and BrdU incorporation assays showed that recombinant mouse NGAL (mNGAL) protein significantly decreased the viability and proliferation of 2L3 cells. Flow cytometry and western blot analyses showed that mNGAL inhibited activation of the ERK and AKT pathways and induced apoptosis and autophagy in 2L3 cells. In addition, a 3D cell culture platform was established to identify cyst progression in 2L3 cells and showed that mNGAL significantly inhibited cyst enlargement in 2L3 cells. Overexpression of secreted mNGAL (pN + LS) and nonsecreted mNGAL (pN − LS) repressed cell proliferation and cyst enlargement in 2L3 cells and had effects on markers involved in proliferation, apoptosis, and autophagy. However, secreted mNGAL had a more pronounced and consistent effect than that of nonsecreted form. These results reveal that secreted mNGAL has stronger ability to inhibit cyst enlargement of ADPKD cells than that of nonsecreted form. These findings could help to identify strategies for the future clinical treatment of ADPKD.

• 3D culture
• ADPKD
• neutrophil gelatinase-associated lipocalin

• Animals
• Cysts
• Lipocalin-2/genetics
• Mice
• Polycystic Kidney, Autosomal Dominant/genetics
• TRPP Cation Channels/genetics

People exposed to liver ischaemia reperfusion (IR) injury often develop acute kidney injury and the combination is associated with significant morbidity and mortality. Molecular mediators released by the liver in response to IR injury are the likely cause of acute kidney injury (AKI) in this setting, but the mediators have not yet been identified. Identifying the mechanism of injury will allow the identification of therapeutic targets which may modulate both liver IR injury and AKI following liver IR injury.

• Liver failure
• Liver transplantation
• Ischaemia-reperfusion injury
• Acute kidney injury
• Liver

Studies suggest a role of the innate immune system, including the activity of neutrophils, in neurodegeneration related to Alzheimer’s disease (AD), but prospective cognitive data remain lacking in humans. We aimed to investigate the predictive relationship between neutrophil-associated inflammatory proteins in peripheral blood and changes in memory and executive function over 1 year in patients with AD.

Participants with AD were identified from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Neutrophil gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), interleukin-8 (IL-8), macrophage inflammatory protein-1 beta (MIP-1β), and tumor necrosis factor (TNF) were assayed by luminex immunofluorescence multiplex assay at baseline. Confirmatory factor analysis was used to test an underlying neutrophil associated plasma inflammatory factor. Composite z-scores for memory and executive function were generated from multiple tests at baseline and at 1 year. A multiple linear regression model was used to investigate the association of the baseline inflammatory factor with changes in memory and executive function over 1 year.

Among AD patients (n = 109, age = 74.8 ± 8.1, 42% women, Mini Mental State Examination [MMSE] = 23.6 ± 1.9), the neutrophil-related inflammatory proteins NGAL (λ = 0.595, p < .001), MPO (λ = 0.575, p < .001), IL-8 (λ = 0.525, p < .001), MIP-1β (λ = 0.411, p = .008), and TNF (λ = 0.475, p < .001) were found to inform an underlying factor. Over 1 year, this inflammatory factor predicted a decline in executive function (β = − 0.152, p = 0.015) but not memory (β = 0.030, p = 0.577) in models controlling for demographics, brain atrophy, white matter hyperintensities, the ApoE ε4 allele, concomitant medications, and baseline cognitive performance.

An inflammatory factor constructed from five neutrophil-related markers in peripheral blood predicted a decline in executive function over 1 year in people with mild AD.

• Alzheimer’s disease
• Executive function
• Inflammation
• Interleukin-8
• Macrophage inflammatory protein-1 beta
• Memory
• Myeloperoxidase
• Neutrophil
• Neutrophil gelatinase-associated Lipocalin
• Tumor necrosis factor