Although tight junctions between human brain microvascular endothelial cells in the blood-brain barrier prevent molecules or cells in the bloodstream from entering the brain, in Alzheimer's disease, peripheral blood monocytes can ''open'' these tight junctions and trigger subsequent transendothelial migration. However, the mechanism underlying this migration is unclear. Here, we found that the CSF2RB, but not CSF2RA, subunit of the granulocyte-macrophage colony-stimulating factor receptor was overexpressed on monocytes from Alzheimer's disease patients. CSF2RB contributes to granulocyte-macrophage colony-stimulating factor-induced transendothelial monocyte migration. Granulocyte-macrophage colony-stimulating factor triggers human brain microvascular endothelial cells monolayer tight junction disassembly by downregulating ZO-1 expression via transcription modulation and claudin-5 expression via the ubiquitination pathway. Interestingly, intracerebral granulocyte-macrophage colony-stimulating factor blockade abolished the increased monocyte infiltration in the brains of APP/PS1 Alzheimer's disease model mice. Our results suggest that in Alzheimer's disease patients, high granulocyte-macrophage colony-stimulating factor levels in the brain parenchyma and cerebrospinal fluid induced blood-brain barrier opening, facilitating the infiltration of CSF2RB-expressing peripheral monocytes across blood-brain barrier and into the brain. CSF2RB might be useful as an Alzheimer's disease biomarker. Thus, our findings will help to understand the mechanism of monocyte infiltration in Alzheimer's disease pathogenesis.
There existed no significant difference of intravesical recurrence and CSS between patients after ONU and LNU. Conclusively, laparoscopic radical nephroureterectomy did not present superiority to open management for patients with UUT-UC.
Different fixation modalities are available for fixation of posterior malleolar fractures (PMFs), but the best method is still unclear. The purpose of this study was to carry out a comparative biomechanical analysis of three commonly used fixation constructs for PMFs using experimental and finite element analysis (FEA). 15 human cadaveric ankle specimens were randomly divided into three groups. Specimens in group-A were fixed with two anteroposterior (AP) lag screws, group-B with two posteroanterior (PA) lag screws, and for group-C, a posterior plate was used. Each model was subjected to axial load. Outcomes included loads for 0.5 mm, 1 mm, 1.5 mm, and 2 mm vertical displacements of posterior fragments were noted. 3D FE models were reconstructed from computed tomography (CT) images and subjected to vertical loads. The model’s stress, fracture step-off, and resultant strains in implants were also studied in 3D FE models. Significantly higher amounts of mean compressive loads were observed to cause the same amount of vertical displacements in plate group (265 ± 60.21 N, 796 ± 57.27 N, 901.18 ± 8.88 N, 977.26 ± 13.04 N) than AP (102.7 ± 16.78 N, 169.5 ± 19.91 N, 225.32 ± 15.92 N, 269.32 ± 17.29 N) and PA (199.88 ± 31.43 N, 362.80 ± 28.46 N, 431.3 ± 28.12 N, 541.86 ± 36.05 N) lag screws respectively (P < 0.05). Simulated micro-motion analysis demonstrated that fracture step-off values in plate group (0.03 ± 0.001 mm, 0.06 ± 0.003 mm and 0.13 ± 0.010 mm) were the lowest among the three groups (P < 0.001). The cancellous bone showed the highest amount of stress in AP and PA lag groups respectively, whereas the lowest stress was noted in the plate-group. This biomechanical study concluded that posterior plating is biomechanically the most stable fixation construct for PMFs fixation. AP and PA lag screws with higher bone stress and fracture step-off values have a high tendency of bone cut-through and loss of fixation respectively.
PIEBV+ NK/T-LPD may be difficult to differentiate from IBD or TB owing to overlapping endoscopic and pathological findings. Early identification of EBV reactivation in tissue samples is essential for the accurate diagnosis.
Hydrogen sulfide (H 2 S) is a physiologically important gas transmitter that serves various biological functions in the body, in a manner similar to that of carbon monoxide and nitric oxide. cystathionine-β-synthase, cystathionine-γ-lyase and cysteine transaminase/3-mercaptopyruvate sulphotransferase are important enzymes involved H 2 S production in vivo, and the mitochondria are the primary sites of metabolism. it has been reported that H 2 S serves an important physiological role in the kidney. under disease conditions, such as ischemia-reperfusion injury, drug nephrotoxicity and diabetic nephropathy, H 2 S serves an important role in both the occurrence and development of the disease. The present review aimed to summarize the production, metabolism and physiological functions of H 2 S, and the progress in research with regards to its role in renal injury and renal fibrosis in recent years.
Contents1. introduction 2. General physicochemical properties of H 2 S 3. Generation and metabolism of H 2 S 4. Physiological role of H 2 S in the kidney 5. role of H 2 S in renal disease 6. conclusions
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