Zobrazení zdroje stránky Bermanholck5145

Our findings confirm that Pocillopora corals activate conserved immune factors in response to LPS and identify transcription factors coordinating Pocillopora corals' immune responses. Additionally, the strong effect of coral genotype on gene expression and bacteria communities highlights the importance of coral genotype in the investigation of coral host-microbe interactions. Drug-induced kidney injury (DIKI) is a frequent occurrence in nonclinical drug development. It is well established that novel urine kidney safety biomarkers will outperform urea nitrogen (BUN) and serum creatinine (sCr) for monitoring direct drug injury to the kidney across numerous compounds spanning diverse mechanisms and efforts are underway for a formal regulatory clinical qualification. However, it remains unclear how these novel biomarkers will perform under prerenal azotemia when BUN and sCr are elevated but no intra-renal injury is suspected. This lack of knowledge is largely due to the dearth of such nonclinical animal models. We report here that treatment of dogs with a potent antihypertensive compound MK-5478 at a suprapharmacologic dose for up to 9 days results in the development of prerenal azotemia and, in some dogs, kidney toxicity through the dual sustained effects of MK-5478 as a nitric oxide donor and an angiotensin II receptor blocker (ARB). While conventional serum biomarkers BUN, and often sCr as well, were highly elevated in these dogs with or without kidney damage, urine kidney biomarkers clusterin (CLU) and neutrophil gelatinase-associated lipocalin (NGAL) showed increases only in dogs with kidney histopathologic changes following the sustained period of prerenal azotemia. Urine albumin (ALB) and total protein also tracked with kidney lesions but with less sensitivity. Thus, we present evidence for the first time that urine kidney safety biomarkers used together with BUN and sCr can distinguish intra-renal injury among dogs with prerenal azotemia while the conventional serum biomarkers alone are ambiguous, either being interpreted as false positives of kidney injury, or dismissed under circumstances as benign without appreciation for a threshold of impending injury. Intervertebral disc degeneration (IDD) is one of the main causes of low back pain, which seriously reduces the quality of life of patients and places a heavy economic burden on their families. Cellular senescence is considered to be an important factor leading to IDD, and inflammatory response, oxidative stress, and mitochondrial dysfunction are closely related to intervertebral disc (IVD) senescence. Therefore, inhibition of the inflammatory response and oxidative stress, along with maintaining mitochondrial function, may be useful in treating IDD. The sirtuins are a family of evolutionarily conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, which are the major molecules mediating life extension or delay of aging-related diseases. The sirtuin protein family consist of seven members (SIRT1 - 7), which are mainly involved in various aging-related diseases by regulating inflammation, oxidative stress, and mitochondrial function. Among them, SIRT1, SIRT2, SIRT3, and SIRT6 are closely related to IDD. In addition, some activators of sirtuin proteins, such as resveratrol, melatonin, magnolol, 1,4-dihydropyridine (DHP), SRT1720, and nicotinamide mononucleotide (NMN), have been evaluated in preclinical studies for their effects in preventing IDD. This review described the biological functions of sirtuins and the important roles of SIRT1, SIRT2, SIRT3, and SIRT6 in IDD by regulating oxidative stress, inflammatory response, and mitochondrial function. In addition, we introduce the status of some sirtuin activators in IDD preclinical studies. This review will provide a background for further clarification of the molecular mechanism underlying IDD and the development of potential therapeutic drugs. V.BACKGROUND Oxidative stress is now recognized to be an important therapeutic target in kidney diseases. However, there are currently no biomarkers that can be used clinically to diagnose renal oxidative stress. METHODS A rapid assay system for urinary thioredoxin 1, an oxidative stress-dependent biomarker of acute kidney injury (AKI), was developed as a chemiluminescence enzyme immunoassay and validated analytically and clinically. RESULTS Analytic evaluation revealed that hemolytic hemoglobin caused measurements to be abnormally high, above the detectable range. However, urine sediment containing red blood cells did not affect the measurements. Assays using our proposed chemiluminescence enzyme immunoassay were completed within as little as 6 min, whereas a conventional ELISA &gt;4 h. Aciduria less then pH 6.0 led to a significant underestimation of thioredoxin 1 concentrations. However, the effects of aciduria were completely reversible with use of a buffer developed for pH adjustment. Urinary thioredoxin 1 was increased in patients with AKI, but was unaffected by extrarenal oxidative stress diseases, including hypoxemia and myocardial infarction, or by chronic kidney disease in which serum creatinine concentrations were comparable. CONCLUSIONS These results suggest that the chemiluminescent enzyme immunoassay system for urinary thioredoxin 1 enables rapid and specific diagnosis of AKI associated with oxidative stress. V.Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. [https://www.selleckchem.com/products/Cediranib.html see more] We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.