SGLT2 expression in human vasculature and heart correlates with low-grade inflammation and causes eNOS-NO/ROS imbalance.

Aims: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a cardioprotective effect in heart failure and myocardial infarction, pathologies often associated with low-grade inflammation. This cross-sectional study aims to investigate whether low-grade inflammation regulates SGLT2 expression and function in human vasculature, heart, and endothelial cells (ECs).

Methods And Results: Human internal thoracic artery (ITA), left ventricle (LV) specimens, and cultured porcine coronary artery ECs were used.

Engineering poly(dehydroalanine)-based gels droplet-based microfluidics: from bulk to microspheres.

Biomedical applications such as drug delivery, tissue engineering, and functional surface coating rely on switchable adsorption and desorption of specialized guest molecules. Poly(dehydroalanine), a polyzwitterion containing pH-dependent positive and negative charges, shows promise for such reversible loading, especially when integrated into a gel network. Herein, we present the fabrication of poly(dehydroalanine)-derived gels of different size scales and evaluate them with respect to their practical use in biomedicine.

Microgels with Immobilized Glycosyltransferases for Enzymatic Glycan Synthesis.

Glycans, composed of linked monosaccharides, play crucial roles in biology and find diverse applications. Enhancing their enzymatic synthesis can be achieved by immobilizing enzymes on materials such as microgels. Here, we present microgels with immobilized glycosyltransferases, synthesized through droplet microfluidics, immobilizing enzymes either via encapsulation or postattachment.

Metabolic Analysis and Renal Protective Effects of Linagliptin and Empagliflozin in Alport Syndrome.

Key Points: Linagliptin reduces kidney function decline and extends lifespan in Alport syndrome mice. Inhibiting the generation of glucose metabolites could serve as a potential therapeutic strategy for the treatment of Alport syndrome.

Background: We previously demonstrated that empagliflozin (Empa), a sodium-glucose cotransporter-2 inhibitor, reduces intrarenal lipid accumulation and slows kidney function decline in experimental Alport syndrome (AS).

Quality assessment of glucose measurement with regard to epidemiology and clinical management of diabetes mellitus in Germany.

Background: During the last decade, Germany has seen an increased prevalence and a redistribution from undetected to diagnosed diabetes mellitus. Due to this substantial epidemiological development, the number of people with documented type 2 diabetes was 8.7 million in 2022.

High-resolution rectoscopy using MHz optical coherence tomography: a step towards real time 3D endoscopy.

Colonoscopy and endoscopic ultrasound play pivotal roles in the assessment of rectal diseases, especially rectal cancer and inflammatory bowel diseases. Optical coherence tomography (OCT) offers a superior depth resolution, which is a critical factor for individualizing the therapeutic concept and evaluating the therapy response. We developed two distinct rectoscope prototypes, which were integrated into a 1300 nm MHz-OCT system constructed at our facility.

SGLT2 inhibition promotes glomerular repopulation by cells of renin lineage in experimental kidney disease.

Aim: Sodium glucose co-transporter-2 (SGLT2) inhibitors stimulate renal excretion of sodium and glucose and exert renal protective effects in patients with (non-)diabetic chronic kidney disease (CKD) and may as well protect against acute kidney injury (AKI). The mechanism behind this kidney protective effect remains unclear. Juxtaglomerular cells of renin lineage (CoRL) have been demonstrated to function as progenitors for multiple adult glomerular cell types in kidney disease.

COVID-19 promotes endothelial dysfunction and thrombogenicity: role of proinflammatory cytokines/SGLT2 prooxidant pathway.

Background: COVID-19 is associated with an increased risk of cardiovascular complications. Although cytokines have a predominant role in endothelium damage, the precise molecular mechanisms are far from being elucidated.

Objectives: The present study hypothesized that inflammation in patients with COVID-19 contributes to endothelial dysfunction through redox-sensitive SGLT2 overexpression and investigated the protective effect of SGLT2 inhibition by empagliflozin.

Compartmentalized Polyampholyte Microgels by Depletion Flocculation and Coacervation of Nanogels in Emulsion Droplets.

In pH-responsive drug carriers, the distribution of charges has been proven to affect delivery efficiency but is difficult to control and verify. Herein, we fabricate polyampholyte nanogel-in-microgel colloids (NiM-C) and show that the arrangement of the nanogels (NG) can easily be manipulated by adapting synthesis conditions. Positively and negatively charged pH-responsive NG are synthesized by precipitation polymerization and labelled with different fluorescent dyes.

Predicting Time to and Average Quality of Future Offers for Kidney Transplant Candidates Declining a Current Deceased Donor Kidney Offer: A Retrospective Cohort Study.

Background: At the time a kidney offer is made by an organ donation organization (ODO), transplant physicians must inform candidates on the and of accepting or declining the offer. Although physicians have a general idea of expected wait time to kidney transplantation by blood group in their ODO, there are no tools that provide quantitative estimates based on the allocation score used and donor/candidate characteristics. This limits the shared decision-making process at the time of kidney offer as (1) the consequences of declining an offer in terms of wait-time prolongation cannot be provided and (2) the quality of the current offer cannot be compared with that of offers that could be made to the specific candidate in the future.

Effects of body orientation and direction of movement on a knee joint angle reproduction test in healthy subjects: An experimental study.

Background: Joint position sense test assess patient mobility and proprioceptive ability. Yet, application used under different conditions may biases reproduction error resulting in different therapeutic consequences.

Objective: To investigate knee angle reproduction test under different test conditions.

Cardioprotective Effect of Empagliflozin and Circulating Ketone Bodies During Acute Myocardial Infarction.

Background: SGLT2i (sodium-glucose cotransporter-2 inhibitors) improve clinical outcomes in patients with heart failure, but the mechanisms of action are not completely understood. SGLT2i increases circulating levels of ketone bodies, which has been demonstrated to enhance myocardial energetics and induce reverse ventricular remodeling. However, the role of SGLT2i or ketone bodies on myocardial ischemia reperfusion injury remains in the dark.

The SGLT2 inhibitor empagliflozin improves cardiac energy status via mitochondrial ATP production in diabetic mice.

Empagliflozin, a sodium-glucose co-transporter 2 inhibitor developed, has been shown to reduce cardiovascular events in patients with type 2 diabetes and established cardiovascular disease. Several studies have suggested that empagliflozin improves the cardiac energy state which is a partial cause of its potency. However, the detailed mechanism remains unclear.

Parahydrogen-Induced Polarization of a Labeled, Cancer-Targeting DNA Aptamer.

Enhancing NMR signals of biomacromolecules by hyperpolarization offers exciting opportunities for diagnostic applications. However, their hyperpolarization via parahydrogen remains challenging as specific catalytic interactions are required, which are difficult to tune due to the large size of the biomolecule and its insolubility in organic solvents. Herein, we show the unprecedented hyperpolarization of the cancer-targeting DNA aptamer AS1411.

The automized fracture edge detection and generation of three-dimensional fracture probability heat maps.

With proven impact of statistical fracture analysis on fracture classifications, it is desirable to minimize the manual work and to maximize repeatability of this approach. We address this with an algorithm that reduces the manual effort to segmentation, fragment identification and reduction. The fracture edge detection and heat map generation are performed automatically.

Surgical Management of Emphysematous Gastritis in a Postpartum Female: A Case Report and Literature Review.

Emphysematous gastritis is a form of gastritis characterized by both gastric inflammation and the presence of intramural gas. Its occurrence is rare, and its presentation is non-specific. Consequently, no definitive guidelines for management have been outlined.

The membrane-associated protein 17 (MAP17) is up-regulated in response to empagliflozin on top of RAS blockade in experimental diabetic nephropathy.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have proven to delay diabetic kidney disease (DKD) progression on top of the standard of care with the renin-angiotensin system (RAS) blockade. The molecular mechanisms underlying the synergistic effect of SGLT2i and RAS blockers is poorly understood. We gave a SGLT2i (empagliflozin), an angiotensin-converting enzyme inhibitor (ramipril), or a combination of both drugs for 8 weeks to diabetic (db/db) mice.

Enhanced Cardiorenal Protective Effects of Combining SGLT2 Inhibition, Endothelin Receptor Antagonism and RAS Blockade in Type 2 Diabetic Mice.

Treatments with sodium-glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin-angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks.

Therapeutic effects of Fc gamma RIV inhibition are mediated by selectively blocking immune complex-induced neutrophil activation in epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is a subepidermal autoimmune bullous disease caused by autoantibodies targeting type VII collagen (COL7). It is characterized by inflammation and subepidermal blistering mainly through immune complex (IC)-mediated activation of neutrophils. In experimental EBA, binding of neutrophils to ICs in the skin and induction of clinical disease depends on the expression of the Fc gamma receptor (FcγR) IV.

Intravital imaging of mucus transport in asthmatic mice using microscopic optical coherence tomography.

Asthma is one of the most common chronic diseases. Mucus overproduction is consistently linked to asthma morbidity and mortality. Despite the knowledge of the importance of mucus, little data exist on how mucus is transported in asthma and the immediate effects of therapeutic intervention.

Dynamic microscopic optical coherence tomography to visualize the morphological and functional micro-anatomy of the airways.

In the imaging of airway tissue, optical coherence tomography (OCT) provides cross-sectional images of tissue structures, shows cilia movement and mucus secretion, but does not provide sufficient contrast to differentiate individual cells. By using fast sequences of microscopic resolution OCT (mOCT) images, OCT can use small signal fluctuations to overcome lack in contrast and speckle noise. In this way, OCT visualizes airway morphology on a cellular level and allows the tracking of the dynamic behavior of immune cells, as well as mucus transport and secretion.