Early neutrophil gelatinase-associated lipocalin (NGAL) measurement could rule out future acute kidney injury in patients with acute coronary syndrome-Prospective observational study.

Background And Aims: The diagnosis of acute kidney injury (AKI) is of importance among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). It is often delayed given the need in serial measurements of creatinine or other serum markers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proven marker for AKI, although its role as an early predictor in this setting was scarcely addressed before and was the aim of our study.

Cognitive dysfunction in early experimental metabolic dysfunction-associated steatotic liver disease is associated with systemic inflammation and neuroinflammation.

Background & Aims: Cognitive dysfunction is an increasingly recognised manifestation of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanistic link remains unclear. The aim of this study was to investigate the hypothesis that experimental MASLD leads to cognitive dysfunction via systemic inflammation and neuroinflammation.

Methods: Twenty male Sprague Dawley rats were randomised to a high-fat high-cholesterol (HFHC) diet to induce MASLD, or a standard diet (n = 10/group), for 16 weeks.

Influence of Microgravity on Apoptosis in Cells, Tissues, and Other Systems In Vivo and In Vitro.

All life forms have evolved under the constant force of gravity on Earth and developed ways to counterbalance acceleration load. In space, shear forces, buoyance-driven convection, and hydrostatic pressure are nullified or strongly reduced. When subjected to microgravity in space, the equilibrium between cell architecture and the external force is disturbed, resulting in changes at the cellular and sub-cellular levels (e.

Low Interleukin-22 Binding Protein Is Associated With High Mortality in Alcoholic Hepatitis and Modulates Interleukin-22 Receptor Expression.

Introduction: In alcoholic hepatitis (AH), high interleukin (IL)-22 production is associated with disease improvement, purportedly through enhanced infection resistance and liver regeneration. IL-22 binding protein (BP) binds and antagonizes IL-22 bioactivity, but data on IL-22BP in liver disease suggest a complex interplay. Despite the scarcity of human data, IL-22 is in clinical trial as treatment of AH.

A Human Randomized Controlled Trial Comparing Metabolic Responses to Single and Repeated Hypoglycemia in Type 1 Diabetes.

Aims: Hypoglycemia hinders optimal glycemic management in type 1 diabetes (T1D). Long diabetes duration and hypoglycemia impair hormonal counter-regulatory responses to hypoglycemia. Our study was designed to test whether (1) the metabolic responses and insulin sensitivity are impaired, and (2) whether they are affected by short-lived antecedent hypoglycemia in participants with T1D.

The impact of minimal invasive extracorporeal circulation on postoperative kidney function.

Introduction: Acute kidney injury following cardiac surgery is a frequent complication associated with increased mortality and morbidity. Minimal invasive extracorporeal circulation is suggested to preserve postoperative renal function. The aim of this study was to assess the impact of minimal invasive versus conventional extracorporeal circulation on early postoperative kidney function.

Soluble Klotho: a possible predictor of quality of life in acromegaly patients.

Purpose: Although quality of life (QoL) is improved in patients with acromegaly after disease control, QoL correlates only weakly with traditional biomarkers. Our objective is to investigate a potential relation between the new serum biomarker soluble Klotho (sKlotho), GH and insulin-like growth factor 1 (IGF-1) levels, and QoL.

Methods: In this prospective cohort study, we investigated 54 acromegaly patients biochemically well-controlled on combination treatment with first-generation somatostatin receptor ligands (SRLs) and pegvisomant (PEGV) at baseline and 9 months after switching to pasireotide LAR (PAS-LAR; either as monotherapy, n = 28; or in combination with PEGV, n = 26).

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells.

Prostate cancer is one of the leading causes of cancer mortality in men worldwide. An unusual but unique environment for studying tumor cell processes is provided by microgravity, either in space or simulated by ground-based devices like a random positioning machine (RPM). In this study, prostate adenocarcinoma-derived PC-3 cells were cultivated on an RPM for time periods of 3 and 5 days.

Drug-Induced Hypertension Caused by Multikinase Inhibitors (Sorafenib, Sunitinib, Lenvatinib and Axitinib) in Renal Cell Carcinoma Treatment.

This paper reviews current treatments for renal cell carcinoma/cancer (RCC) with the multikinase inhibitors (MKIs) sorafenib, sunitinib, lenvatinib and axitinib. Furthermore, it compares these drugs regarding progression-free survival, overall survival and adverse effects (AE), with a focus on hypertension. Sorafenib and sunitinib, which are included in international clinical guidelines as first- and second-line therapy in metastatic RCC, are now being challenged by new-generation drugs like lenvatinib and axitinib.

Tyrosine Kinase Inhibitor-Induced Hypertension: Role of Hypertension as a Biomarker in Cancer Treatment.

Cancer treatment is an area of continuous improvement. Therapy is becoming more targeted and the use of anti-angiogenic agents in multiple cancers, specifically tyrosine kinase inhibitors (TKIs), has demonstrated prolonged survival outcomes compared with previous drugs. Therefore, they have become a well-established part of the treatment.

Key Proteins Involved in Spheroid Formation and Angiogenesis in Endothelial Cells After Long-Term Exposure to Simulated Microgravity.

Background/aims: Cardiovascular complications are common in astronauts returning from a prolonged spaceflight. These health problems might be driven by complex modulations of gene expression and protein synthesis in endothelial cells (ECs). Studies on the influence of microgravity on phenotype, growth pattern and biological processes of ECs can help to understand these complications.

Effects of Prednisolone on Serum and Tissue Fluid IGF-I Receptor Activation and Post-Receptor Signaling in Humans.

Context: Short-term glucocorticoid exposure increases serum insulinlike growth factor I (IGF-I) concentrations but antagonizes IGF-I tissue signaling. The underlying mechanisms remain unknown.

Objective: To identify at which levels glucocorticoid inhibits IGF-I signaling.

Hypertension Caused by Lenvatinib and Everolimus in the Treatment of Metastatic Renal Cell Carcinoma.

Multikinase inhibitors (MKI) and mammalian target of rapamycin (mTOR) inhibitors prolong progression-free (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC) by reducing angiogenesis and tumor growth. In this regard, the MKI lenvatinib and the mTOR inhibitor everolimus proved effective when applied alone, but more effective when they were administered combined. Recently, both drugs were included in clinical trials, resulting in international clinical guidelines for the treatment of mRCC.

Neutrophil gelatinase-associated lipocalin as a risk marker in cardiovascular disease.

Neutrophil gelatinase-associated lipocalin (NGAL) is a promising diagnostic biomarker of early acute kidney injury. Increasing evidence suggests that NGAL may also be involved in inflammatory processes in cardiovascular disease. NGAL modulates the enzymatic activity of matrix metalloproteinase-9 (MMP-9), which is an important mediator of plaque instability in atherosclerosis.

Effects and Side Effects of Using Sorafenib and Sunitinib in the Treatment of Metastatic Renal Cell Carcinoma.

In recent years, targeted therapies have proven beneficial in terms of progression-free survival (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC). The tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib are included in international clinical guidelines as first-line and second-line therapy in mRCC. Hypertension is an adverse effect of these drugs and the degree of hypertension associates with the anti-tumour effect.

Long-Term Ethanol Exposure Decreases the Endotoxin-Induced Hepatic Acute Phase Response in Rats.

Background: Long-term excessive alcohol intake predisposes to infectious diseases. The hepatic acute-phase response is a component of the innate immune system and is part of the first line of defense against invading pathogens, which may be compromised by alcohol. We aimed to investigate whether an induced acute-phase response is impaired in long-term ethanol (EtOH)-fed rats.

Reduced Expression of Cytoskeletal and Extracellular Matrix Genes in Human Adult Retinal Pigment Epithelium Cells Exposed to Simulated Microgravity.

Background/aims: Microgravity (µg) has adverse effects on the eye of humans in space. The risk of visual impairment is therefore one of the leading health concerns for NASA. The impact of µg on human adult retinal epithelium (ARPE-19) cells is unknown.

PAPP-A, IGFBP-4 and IGF-II are secreted by human adipose tissue cultures in a depot-specific manner.

Objective: Adipose tissue secretes pregnancy-associated plasma protein-A (PAPP-A), which may increase local IGF action through cleavage of IGF-binding protein-4 (IGFBP-4). We tested whether this mechanism was operational in human visceral and subcutaneous adipose tissue (i.e.

Growth Hormone and Insulin Signaling in Acromegaly: Impact of Surgery Versus Somatostatin Analog Treatment.

Context: Somatostatin analogs (SAs) used in acromegaly to suppress GH secretion and tumor growth also suppress insulin secretion and may impact GH signaling.

Objective: To compare GH and insulin signaling after iv GH exposure in acromegalic patients controlled by surgery (n = 9) or SA (n = 9).

Design: Each patient was studied for 3 hours after an overnight fast (t = -60 to 120 minutes).

Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats.

Aim: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats.

Methods: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate (0.02 mg/kg) or free dexamethasone (0.

Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction.

Background/aims: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a marker for acute kidney injury and cardiovascular outcome. However, the relative importance of inflammation versus kidney function on plasma NGAL levels is uncertain, making the interpretation of plasma NGAL unclear. Accordingly, we investigated the relationship between plasma NGAL, inflammation and kidney function in patients with myocardial infarction (MI).

Identifications of novel mechanisms in breast cancer cells involving duct-like multicellular spheroid formation after exposure to the Random Positioning Machine.

Many cell types form three-dimensional aggregates (MCS; multicellular spheroids), when they are cultured under microgravity. MCS often resemble the organ, from which the cells have been derived. In this study we investigated human MCF-7 breast cancer cells after a 2 h-, 4 h-, 16 h-, 24 h- and 5d-exposure to a Random Positioning Machine (RPM) simulating microgravity.

Pathways Regulating Spheroid Formation of Human Follicular Thyroid Cancer Cells under Simulated Microgravity Conditions: A Genetic Approach.

Microgravity induces three-dimensional (3D) growth in numerous cell types. Despite substantial efforts to clarify the underlying mechanisms for spheroid formation, the precise molecular pathways are still not known. The principal aim of this paper is to compare static 1g-control cells with spheroid forming (MCS) and spheroid non-forming (AD) thyroid cancer cells cultured in the same flask under simulated microgravity conditions.

Mechanisms of three-dimensional growth of thyroid cells during long-term simulated microgravity.

Three-dimensional multicellular spheroids (MCS) of human cells are important in cancer research. We investigated possible mechanisms of MCS formation of thyroid cells. Both, normal Nthy-ori 3-1 thyroid cells and the poorly differentiated follicular thyroid cancer cells FTC-133 formed MCS within 7 and 14 days of culturing on a Random Positioning Machine (RPM), while a part of the cells continued to grow adherently in each culture.