Microbiota signatures in type-2 diabetic patients with chronic kidney disease - A Pilot Study

The human microbiota is paramount for normal host physiology. Altered host-microbiome interactions are part of the pathogenesis of numerous common ailments. Currently, much emphasis is placed on the involvement of the microbiome in the pathogenesis of type-2 diabetes mellitus (T2DM), impaired glucose tolerance, and other metabolic disorders (i.e. obesity). Several studies found highly significant correlations of specific intestinal bacteria with T2DM. A better understanding of the role of the microbiome in diabetes and its complications might provide new insights in the development of new therapeutic principles. Our pilot study investigates the microbiota patterns in Romanian type-2 diabetic patients with diabetic kidney disease. Fecal samples were collected from type 2-diabetic patients and healthy controls and further used for bacterial DNA isolation. Using 16 rDNA qRT-PCR, we analyzed phyla abundance (Bacteroidetes, Firmicutes) as well as the relative abundance of specific bacterial groups (Lactobacillus sp., Enterobacteriaceae, Ruminococus sp., Prevotella sp., Faecalibacterium sp., Clostridium coccoides, Clostridium leptum). Our study also investigates the diabetic fungal microbiome for the first time. Furthermore, we report significant correlations between the treatment regimen and microbiota composition in diabetic nephropathy

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Thrombosis and Haemostasis challenges in COVID-19 – Therapeutic perspectives of heparin and tissue-type plasminogen activator and potential toxicological reactions-a mini review

The coronavirus disease (COVID)-19 pandemic is a major challenge for the health systems worldwide. Acute respiratory distress syndrome (ARDS), is one of the most common complications of the COVID-19 infection. The activation of the coagulation system plays an important role in the pathogenesis of ARDS. The development of lung coagulopathy involves thrombin generation and fibrinolysis inhibition. Unfractionated heparin and its recently introduced counterpart low molecular weight heparin (LMWH), are widely used anticoagulants with a variety of clinical indications allowing for limited and manageable physio-toxicologic side effects while the use of protamine sulfate, heparin's effective antidote, has made their use even safer. Tissue-type plasminogen activator (tPA) is approved as intravenous thrombolytic treatment. The present narrative review discusses the use of heparin and tPA in the treatment of COVID-19-induced ARDS and their related potential physio-toxicologic side effects. The article is a quick review of articles on anticoagulation in COVID infection and the potential toxicologic reactions associated with these drugs. © 2021 Elsevier Lt

C-terminal processing of collagen XVII induces neoepitopes for linear IgA dermatosis autoantibodies [an abstract of dissertation and a summary of dissertation review]

配架番号：235

Predictors associated with treatment initiation and switch in a real-world chronic hepatitis B population from five European countries

International audienc

Halmyris: Geoarchaeology of a fluvial harbour on the Danube Delta (Dobrogea, Romania)

In Northern Dobrogea, north of the Dunavăţ promontory, the Roman fortress of Halmyris was founded in the late 1st century AD on a Getic settlement dating to the middle of the 1st millennium BC, probably associated with a Greek emporium of the Classical and Hellenistic periods. At the time of the foundation of Halmyris, the Danube delta had already prograded several kilometres to the east leading to the progressive retreat of the sea and the formation of a deltaic plain characterised by numerous lakes and river channels. Here, we present the results of a multiproxy study combining sedimentology and palaeoecology to (1) understand the evolution of fluvial landscapes around Halmyris since ca. 8000 years BP and (2) identify the fluvial palaeoenvironments close to the city in Getic/Greek and Roman times, in order to locate and characterise the waterfront and the harbour. Our overriding objective was to improve understanding of human–environment relations in river delta settings. We demonstrate that Halmyris, protected by the Danubian floods due to its location on a palaeo-cliff top, had direct access to the river. A secondary channel of the Saint George, flowing north of the site, has been elucidated between the 7th century BC and the 7th century AD and could have been used as a natural harbour