Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly with or without focal and segmental glomerulosclerosis lesions. Isothiocyanate sulforaphane (SFN) can protect kidneys from ...ORG-related damages. In this study, we investigated the effects of SFN as a preventive therapy or intervention for ORG to reveal its mechanism of action.
We established a mouse obesity model with preventive SFN or N-acetylcysteine treatment for 2 months. Thereafter, we used nuclear factor erythroid 2-related factor 2-deficient (Nrf2−/−) and wild type mice in our ORG model with SFN treatment. Finally, we generated a corresponding mouse podocyte model in vitro. The body weight, wet weight of perirenal-and peritesticular fat, and urinary albumin/creatinine ratio were assessed. We used periodic acid–Schiff staining and electron microscopy to assess the function of the kidneys and podocytes. In addition, we evaluated the expression of Nrf2 and podocyte-specific proteins by western blotting.
Treatment with SFN reduced body weight, organ-associated fat weight, and urinary albumin/creatinine ratio in both the preventive treatment and disease intervention regimens. SFN treated mice exhibited higher expression levels of podocyte-specific proteins and better podocyte function. However, treatment with SFN did not affect these parameters in obese Nrf2−/− mice. Light chain 3 of microtubule-associated protein 1-II and metallothionein had higher expression in the wild type than in the Nrf2−/− mice.
Treatment with SFN limited ORG-induced damage by enhancing podocyte autophagy via Nrf2.
•Sulforaphane suppresses ORG damage in preventive treatment and disease intervention regimens.•Nrf2−/− mice were not protected by sulforaphane from obesity-induced damage.•Sulforaphane enhanced autophagy in podocytes by regulating Nrf2 expression.
Design of selective sensors for a specific analyte in blood serum, which contains a large number of proteins, small molecules, and ions, is important in clinical diagnostics. While metal and ...polymeric nanoparticle conjugates have been used as sensors, small molecular assemblies have rarely been exploited for the selective sensing of a protein in blood serum. Herein we demonstrate how a nonspecific small molecular fluorescent dye can be empowered to form a selective protein sensor as illustrated with a thiol-sensitive near-IR squaraine (Sq) dye (λabs= 670 nm, λem= 700 nm). The dye self-assembles to form nonfluorescent nanoparticles (D h = 200 nm) which selectively respond to human serum albumin (HSA) in the presence of other thiol-containing molecules and proteins by triggering a green fluorescence. This selective response of the dye nanoparticles allowed detection and quantification of HSA in blood serum with a sensitivity limit of 3 nM. Notably, the Sq dye in solution state is nonselective and responds to any thiol-containing proteins and small molecules. The sensing mechanism involves HSA specific controlled disassembly of the Sq nanoparticles to the molecular dye by a noncovalent binding process and its subsequent reaction with the thiol moiety of the protein, triggering the green emission of a dormant fluorophore present in the dye. This study demonstrates the power of a self-assembled small molecular fluorophore for protein sensing and is a simple chemical tool for the clinical diagnosis of blood serum.
Giriş: İnflamasyon kanser gelişimini kolaylaştırmanın yanı sıra birçok kanser tipinde kötü prognozla da ilişkilidir. Albümin ve globülin inflamasyonu yansıtan belirteçlerden ikisidir. Albüminin ...özellikle inflamasyon dışı birçok nedenden etkilenebileceği için albümin globülin oranının inflamasyonu yansıtmada daha başarılı olacağı gösterilmiştir. Biz bu çalışmada albümin globülin oranın (AGO) küçük hücreli akciğer kanserinde (KHAK) prognostik öneminin belirlenmesi ve diğer inflamatuar parametrelerle ilişkisinin saptanmasını amaçladık. Materyal ve Metot: Retrospektif olarak 2014-2018 yılları arasından tanı almış KHAK hastaları çalışmaya dâhil edildi. Tanı anındaki albümin globüline bölünerek AGO bulundu. Medyan değer olan 1,2 AGO için eşik değer olarak kabul edildi. Bulgular: Toplam 81 hasta çalışmaya dâhil edildi. Hastaların %40,30’ü AGO < 1,2 olarak saptanırken, % 59,30’ünün ise AGO ≥ 1,2 olarak bulundu. Her iki grup hasta özellikleri açısından benzerdi. AGO ile nötrofil lenfosit oranı ve platelet lenfosit oranı arasında istatistiksel anlamlı ters korelasyon saptandı. AGO ≥ 1,2 olan grupta hem progresyonsuz sağkalım hem de genel sağkalım istatistiksel olarak daha uzundu. Sonuç: AGO hem kolay uygulanabilir hem de ucuz bir belirteç olması nedeniyle KHAK’de prognostik belirteç olarak kullanılabilir.
Recommended treatment for type 1 hepatorenal syndrome consists of albumin and vasoconstrictor. The optimal albumin dose remains poorly characterized. This meta-analysis aimed to determine the impact ...of albumin dose on treatment outcomes.
Clinical studies of type 1 hepatorenal syndrome treatment with albumin and vasoconstrictor were sought. Search terms included: hepatorenal syndrome; albumin; vasoconstrictor; terlipressin; midodrine; octreotide; noradrenaline; and norepinephrine. A meta-analysis was performed of hepatorenal syndrome reversal and survival in relation to albumin dose.
Nineteen clinical studies with 574 total patients were included, comprising 8 randomized controlled trials, 8 prospective studies and 3 retrospective studies. The pooled percentage of patients achieving hepatorenal syndrome reversal was 49.5% (95% confidence interval, 40.0-59.1%). Increments of 100 g in cumulative albumin dose were accompanied by significantly increased survival (hazard ratio, 1.15; 95% confidence interval, 1.02-1.31; p = 0.023). A non-significant increase of similar magnitude in hepatorenal syndrome reversal was also observed (odds ratio, 1.15; 95% confidence interval, 0.97-1.37; p = 0.10). Expected survival rates at 30 days among patients receiving cumulative albumin doses of 200, 400 and 600 g were 43.2% (95% confidence interval, 36.4-51.3%), 51.4% (95% confidence interval, 46.3-57.1%) and 59.0% (95% confidence interval, 51.9-67.2), respectively. Neither survival nor hepatorenal syndrome reversal was significantly affected by vasoconstrictor dose or type, treatment duration, age, baseline serum creatinine, bilirubin or albumin, baseline mean arterial pressure, or study design, size or time period.
This meta-analysis suggests a dose-response relationship between infused albumin and survival in patients with type 1 hepatorenal syndrome. The meta-analysis provides the best current evidence on the potential role of albumin dose selection in improving outcomes of treatment for type 1 HRS and furnishes guidance for the design of future dose-ranging studies.
Nonalcoholic fatty liver disease （NAFLD） is one of themajor causes of chronic liver injury. NAFLD includes awide range of clinical conditions from simple steatosisto nonalcoholic steatohepatitis ...（NASH）, advancedfibrosis, and liver cirrhosis. The histological findingsof NASH indicate hepatic steatosis and inflammationwith characteristic hepatocyte injury （e.g. , ballooningdegeneration）, as is observed in the patients withalcoholic liver disease. NASH is considered to be apotentially health-threatening disease that can progressto cirrhosis. A liver biopsy remains the most reliablediagnostic method to appropriately diagnose NASH,evaluate the severity of liver fibrosis, and determinethe prognosis and optimal treatment. However, thisinvasive technique is associated with several limitationsin routine use, and a number of biomarkers havebeen developed in order to predict the degree of liverfibrosis. In the present article, we review the currentstatus of noninvasive biomarkers available to estimateliver fibrosis in the patients with NASH. We also discussour recent findings on the use of the glycated albuminto-glycated hemoglobin ratio, which is a new index thatcorrelates to various chronic liver diseases, includingNASH.
The present study reports the biological evaluation of vanadium(V) complexes (1–3) against three different proteins: tyrosinase, acetylcholinesterase (AChE), and human serum albumin (HSA), which were ...studied by spectroscopic techniques and molecular docking. Despite the synthesis and characterization of complexes 1 and 2 having already previously described, complex 3 is a novel dioxidovanadium(V) derivative. Complex 1 can activate both tyrosinase and AChE enzymes in about 11.5 and 47.0%, respectively. On the other hand, complexes 2 and 3 inhibited the same enzymes (1.30 and 46.0% for tyrosinase and 20.0 and 21.9% for AChE, respectively). Molecular docking calculations suggested that the presence of the hydroxyl group in complex 1 is essential to activate tyrosinase enzymes. According to theoretical analysis, hydrogen bonding, van der Waals, and hydrophobic forces are the main binding interactions for each V(V) complex and AChE. Moreover, the interaction between HSA and vanadium(V) complexes occurs via ground-state association, being only enthalpically driven for complexes 1 and 2 and entropically and enthalpically driven for complex 3. The interaction is spontaneous for all samples and the binding modes do not perturb significantly the secondary and surface structures of the albumin. As there are few reported cases in the literature that explore vanadium complexes against these three proteins, the present results may contribute to future studies by offering different scaffolds to design new vanadium(V) complexes in the hyperpigmentation process and Alzheimer's disease.
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•Structural characterization analysis of vanadium(V) complexes;•Investigation of HSA-binding properties of vanadium(V) complexes;•Tyrosinase and acetylcholinesterase enzyme inhibition by vanadium(V) derivatives;
The current quantitative polymerase chain reaction (QPCR) assay of telomere length measures telomere (T) signals in experimental DNA samples in one set of reaction wells, and single copy gene (S) ...signals in separate wells, in comparison to a reference DNA, to yield relative T/S ratios that are proportional to average telomere length. Multiplexing this assay is desirable, because variation in the amount of DNA pipetted would no longer contribute to variation in T/S, since T and S would be collected within each reaction, from the same input DNA. Multiplexing also increases throughput and lowers costs, since half as many reactions are needed. Here, we present the first multiplexed QPCR method for telomere length measurement. Remarkably, a single fluorescent DNA-intercalating dye is sufficient in this system, because T signals can be collected in early cycles, before S signals rise above baseline, and S signals can be collected at a temperature that fully melts the telomere product, sending its signal to baseline. The correlation of T/S ratios with Terminal Restriction Fragment (TRF) lengths measured by Southern blot was stronger with this monochrome multiplex QPCR method (R² = 0.844) than with our original singleplex method (R² = 0.677). Multiplex T/S results from independent runs on different days were highly reproducible (R² = 0.91).
Background Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy. ...Objective Our primary objective was to determine whether peanut OIT can induce sustained unresponsiveness after withdrawal of OIT. Methods We conducted a pilot clinical trial of peanut OIT at 2 US centers. Subjects age 1 to 16 years were recruited and treated for up to 5 years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg/d peanut protein. Blood was collected at multiple time points. Clinical end points were measured with 5000-mg double-blinded, placebo-controlled food challenges once specific criteria were met. Results Of the 39 subjects originally enrolled, 24 completed the protocol and had evaluable outcomes. Twelve (50%) of 24 successfully passed a challenge 1 month after stopping OIT and achieved sustained unresponsiveness. Peanut was added to the diet. At baseline and the time of challenge, such subjects had smaller skin test results, as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2 and lower ratios of peanut-specific IgE/total IgE compared with subjects not passing. There were no differences in peanut IgG4 levels or functional activity at the end of the study. Conclusions This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated for up to 5 years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin test results and lower allergen-specific IgE levels were predictive of successful outcome.
Fibril Assemblies in Aqueous Whey Protein Mixtures Bolder, Suzanne G; Hendrickx, Hanneke; Sagis, Leonard M. C ...
Journal of agricultural and food chemistry,
06/2006, Volume:
54, Issue:
12
Journal Article
Peer reviewed
Fibril formation in mixtures of whey proteins upon heating at pH 2 was investigated. Fibrils were found to coexist with other structures, such as spherulites. These spherulites consist of radially ...oriented fibrils. At total protein concentrations above 6 wt %, transparent gels were formed. Changing the ratio between the various whey proteins did not affect this gelation concentration as long as β-lactoglobulin (β-lg) was present, suggesting that β-lg was dominant in the gelation. Pure α-lactalbumin and pure bovine serum albumin did not form fibrils, nor did they gel upon heating at pH 2 and 80 °C for up to 10 h. They did however induce a decrease in the β-lg concentration needed for gel formation upon heating at pH 2. Our results suggest that β-lg is the only fibril forming protein at the conditions used and that no mixed fibrils are formed. Keywords: Heat-induced aggregation; heat-set gelation; fibrils; whey proteins; β-lactoglobulin
Yugoslavya'nın daǧılması sürecine eklemlenen son zincir olan Kosova, baǧımsızlık ilanından bu yana siyasal statü tartışmalarıyla yoǧrulan bir ülkedir. Kosova, demografik ve ekonomik anlamda olduǧu ...kadar, ulusal kapasite ve güç unsurları ve bu unsurların algılanış şekli itibarıyla da küçük devlet olma özelliklerini kendisine eklemlemiştir. İzlediǧi dış politika itibarıyla küçük devlet olmanın gerektirdiǧi biçimde hareket ettiǧi söylenebilecek olan Kosova'nın, geleceǧini ABD ve AB'nin bölge stratejilerine entegre ettiǧi de ifade edilebilir. Stratejik kültür ve izlenen genel dış politika kalıpları itibarıyla ortaklaştıǧı belirtilebilecek Kosovalı siyasal aktörlerin birbirlerinden farklılaştıǧı noktalar da bulunmaktadır. Siyasal deǧişimi de beraberinde getiren bu farklılaşmayı inceleyebilmek için de neoklasik realizmin kavramsal çerçevesine başvurmak doǧru bir yaklaşım olabilecektir. Böylece, ideolojik konumlanma, algı ve çıkarların Kosova dış politikasına nasıl yansıdıǧı deǧerlendirilebilecektir.
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