Soluble Urokinase Plasminogen Activator Receptor as a Predictor of All-Cause Death in Patients Undergoing Coronary Angiography at 10-Year Follow-Up.

We aimed to explore the predictive role of soluble urokinase plasminogen activator receptor (suPAR) in patients undergoing coronary angiography by systematically evaluating its association with adverse cardiovascular events at 10 years follow-up. The KORONEF study was a single-center, observational, prospective study with 492 subjects included. In the multivariable Cox regression model, we checked the impact of suPAR, neutrophil elastase, myeloperoxidase, and DNase 1 on long-term outcomes.

Gray-Scale Median in Patients with Symptomatic and Asymptomatic Carotid Atherosclerosis-Risk Factors and Diagnostic Potential.

Background: The identification of clinical factors affecting the gray-scale median (GSM) and determination of GSM diagnostic utility for differentiating between symptomatic and asymptomatic internal carotid artery (ICA) stenosis.

Methods: This study included 45 patients with asymptomatic and 40 patients with symptomatic ICA stenosis undergoing carotid endarterectomy (CEA). Echolucency of carotid plaque was determined using computerized techniques for the GSM analysis.

The Possible Effect of β-Blocker Use on the Circulating MMP-2/TIMP-2 System in Patients with Chronic Kidney Disease on Conservative Treatment.

: The purpose of the study was to determine whether the use of β-adrenoceptor antagonists (β-blockers) can affect metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in patients with chronic kidney disease (CKD) on conservative treatment. : The circulating MMP-2/TIMP-2 system, proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the marker of oxidative stress-Cu/Zn superoxide dismutase (Cu/Zn SOD)-were measured in 23 CKD patients treated with β-blockers [β-blockers (+)] and in 27 CKD patients not receiving the above medication [β-blockers (-)]. : The levels of MMP-2, TIMP-2, and IL-6 were significantly lower in the β-blockers (+) than in the β-blockers (-) group, whereas Cu/Zn SOD concentrations were not affected by β-blocker use.

Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats.

Indoxyl sulfate (IS), an agonist of aryl hydrocarbon receptors (AhR), can accumulate in patients with chronic kidney disease, but its direct effect on bone is not clear. The present study investigated the effect of chronic exposure to low (100 mg/kg b.w.

ONCOBREAST-TEST Is a Quick Diagnostic, Prognostic and Predictive Method of Response to Systemic Treatment.

ONCOBREAST-TEST is a diagnostic and therapeutic procedure that is part of the comprehensive care of a patient with breast cancer.: Chemosensitivity of cancer cells was assessed using the MTT test, morphological assessment of cells, LDH activity in the culture medium, and flow cytometry technique (apoptosis, proliferation, CD24, CD44, GATA3, cytokeratin, Ki-67). Diagnostic tools included panels of simple tests which could be used to accurately predict the chemosensitivity of tumor cells previously isolated from a patient, even before actual chemotherapy.

Vitamin K-Dependent Carboxylation of Osteocalcin in Bone-Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease?

Chronic kidney disease (CKD) commonly occurs with vitamin K (VK) deficiency and impaired bone mineralization. However, there are no data explaining the metabolism of endogenous VK and its role in bone mineralization in CKD. In this study, we measured serum levels of phylloquinone (VK1), menaquinone 4 and 7 (MK4, MK7), and VK-dependent proteins: osteocalcin, undercarboxylated osteocalcin (Glu-OC), and undercarboxylated matrix Gla protein (ucMGP).

Kynurenine Pathway-An Underestimated Factor Modulating Innate Immunity in Sepsis-Induced Acute Kidney Injury?

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and it accounts for about half of the cases of acute kidney injury (AKI). Although sepsis is the most frequent cause of AKI in critically ill patients, its pathophysiological mechanisms are not well understood. Sepsis has the ability to modulate the function of cells belonging to the innate immune system.

Indoleamine 2,3 Dioxygenase 1-The Potential Link between the Innate Immunity and the Ischemia-Reperfusion-Induced Acute Kidney Injury?

Ischemia-reperfusion injury (IRI) is of the most common causes of acute kidney injury (AKI); nevertheless, the mechanisms responsible for both early kidney injury and the reparative phase are not fully recognised. The inflammatory response following ischemia is characterised by the crosstalk between cells belonging to the innate immune system-dendritic cells (DCs), macrophages, neutrophils, natural killer (NK) cells, and renal tubular epithelial cells (RTECs). A tough inflammatory response can damage the renal tissue; it may also have a protective effect leading to the repair after IRI.

Benzophenone-3, a chemical UV-filter in cosmetics: is it really safe for children and pregnant women?

Children and adolescents are particularly vulnerable to skin damage caused by ultraviolet radiation and require intensified photoprotection. Benzophenone-3 (BP-3) belongs to the organic sunscreens, which are widely used in personal care and cosmetic products. However, the impact of BP-3 on human health requires a careful assessment.

Preclinical Toxicity and Safety of MM-129-First-in-Class BTK/PD-L1 Inhibitor as a Potential Candidate against Colon Cancer.

MM-129 is a novel inhibitor targeting BTK/PI3K/AKT/mTOR and PD-L1, as it possesses antitumor activity against colon cancer. To evaluate the safety profile of MM-129, we conducted a toxicity study using the zebrafish and rodent model. MM-129 was also assessed for pharmacokinetics features through an in vivo study on Wistar rats.

Serum PTH, PTH1R/ATF4 pathway, and the sRANKL/OPG system in bone as a new link between bone growth, cross-sectional geometry, and strength in young rats with experimental chronic kidney disease.

The progression of chronic kidney disease (CKD) in children is associated with deregulated parathyroid hormone (PTH), growth retardation, and low bone accrual. PTH can cause both catabolic and anabolic impact on bone, and the activating transcription factor 4 (ATF4), a downstream target gene of PTH, is related to its anabolic effect. Osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) are PTH-dependent cytokines, which may play an important role in the regulation of bone remodeling.

Paracrine Kynurenic Pathway Activation in the Bone of Young Uremic Rats Can Antagonize Anabolic Effects of PTH on Bone Turnover and Strength through the Disruption of PTH-Dependent Molecular Signaling.

Secondary hyperparathyroidism and abnormalities in tryptophan (TRP) metabolism are commonly observed in chronic kidney disease (CKD). The present study aimed to establish potential interactions between endogenous parathyroid hormone (PTH) and activation of the bone kynurenine (KYN) pathway in relation to bone turnover and strength in young rats after one month (CKD-1) and three months (CKD-3) of experimental CKD. TRP, KYN, KYN/TRP ratio and bone turnover markers (BTMs) were measured in trabecular and cortical bone tissue.

MM-129 as a Novel Inhibitor Targeting PI3K/AKT/mTOR and PD-L1 in Colorectal Cancer.

Background And Aims: The purpose of the present study was to examine the pharmacodynamics features of MM-129 (1,2,4-triazine derivative) as a novel promising drug candidate against colon cancer.

Methods: MM-129 was assessed for antitumor activity through an in vivo study on Cby.Cg-Foxn1nu/cmdb mice.

Vitamin K and D Supplementation and Bone Health in Chronic Kidney Disease-Apart or Together?

Vitamin K (VK) and vitamin D (VD) deficiency/insufficiency is a common feature of chronic kidney disease (CKD), leading to impaired bone quality and a higher risk of fractures. CKD patients, with disturbances in VK and VD metabolism, do not have sufficient levels of these vitamins for maintaining normal bone formation and mineralization. So far, there has been no consensus on what serum VK and VD levels can be considered sufficient in this particular population.

Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. The impact of the new pyrazolo[4,3-]tetrazolo[1,5-][1,2,4]triazine sulphonamide () was evaluated against human colon cancer and in zebrafish xenografts. Our results show that this new synthesised compound effectively inhibits cell survival in BTK-dependent mechanism.

Modulation of the Paracrine Kynurenic System in Bone as a New Regulator of Osteoblastogenesis and Bone Mineral Status in an Animal Model of Chronic Kidney Disease Treated with LP533401.

An increase in the peripheral synthesis of serotonin and kynurenine, observed during the chronic kidney disease (CKD) course, is negatively associated with bone health. Serotonin and kynurenine are connected by the common precursor, tryptophan. LP533401 is an inhibitor of peripheral serotonin synthesis.

Inhibition of peripheral serotonin synthesis by LP533401 and disturbances in calciotropic hormones attenuated excessive osteoblastogenesis with simultaneous improvement of bone mineral status in 5/6 nephrectomized rats.

Chronic kidney disease (CKD) is a pathological condition associated with renal osteodystrophy for which there are limited treatment options. Gut-derived serotonin (GDS) is one of the key signaling factors controlling the osteoblast proliferation. Previously, we shown that inhibition of GDS synthesis by LP533401 improved bone mineral status of rats with 5/6 nephrectomy-induced CKD model.

The use of LP533401 as a therapeutic option for renal osteodystrophy affects, renal calcium handling, vitamin D metabolism, and bone health in uremic rats.

Background: Klotho is a key regulator of phosphate and Ca-transport in the kidney. Recently, we showed that treatment with LP533401 improved bone health in rats with chronic kidney disease (CKD) via the normalization of serum phosphate resulting from the reduced renal expression of phosphate cotransporters, including Klotho.

Methods: We evaluated the effect of LP533401 therapy on Klotho-expression-dependent Ca-transporters, renal calcium handling, and the potential consequences for the bone of uremic rats.

The impact of antihypertensive pharmacotherapy on interplay between protein-bound uremic toxin (indoxyl sulfate) and markers of inflammation in patients with chronic kidney disease.

Purpose: Indoxyl sulfate (IS) is one of the most potent uremic toxins involved in chronic kidney disease (CKD) progression, induction of inflammation, oxidative stress, and cardiovascular diseases occurrence. It is proved that hypertension is a common CVD complication and a major death risk factor as well as contributes for decline in a renal function. The aim of our study was to investigate how implementing of antihypertensive therapy impact IS concentrations and the associations between IS and markers of renal function, inflammation and oxidative stress.

Indoxyl Sulfate Promotes Arterial Thrombosis in Rat Model via Increased Levels of Complex TF/VII, PAI-1, Platelet Activation as Well as Decreased Contents of SIRT1 and SIRT3.

Patients suffering from chronic kidney disease (CKD) are at a 20-fold higher risk of dying due to cardiovascular diseases (CVDs), primarily thrombosis following vascular injury. CKD is connected with retention of uremic toxins, especially indoxyl sulfate (IS), which are currently considered as a non-classical CKD-specific risk factor for CVDs. The present study aimed to examine the effect of chronic exposure to IS on the hemostatic system and arterial thrombosis in a model without greater interferences from the uremic milieu consisting of additional uremic toxins.

Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study.

Background: Interactions between the digestive system and the brain functions have become in recent years an important field of psychiatric research. These multidirectional interactions take place in the so called microbiota-gut-brain axis and emerging scientific data indicate to the significant role of microbiota in the modulation of the central nervous system (CNS) including affective and cognitive functions.

Objective: An assessment of psychobiotic and immunomodulatory effects of probiotic bacteria Lactobacillus Plantarum 299v (LP299v) by measuring affective, cognitive functions and biochemical parameters in patients with MDD undergoing treatment with selective serotonin reuptake inhibitors (SSRI).

LP533401 restores bone health in 5/6 nephrectomized rats by a decrease of gut-derived serotonin and regulation of serum phosphate through the inhibition of phosphate co-transporters expression in the kidneys.

LP533401 is an orally bioavailable small molecule that inhibits tryptophan hydroxylase-1, an enzyme responsible for the synthesis of gut-derived serotonin (GDS). Recently, we showed that increased GDS in rats with chronic kidney disease (CKD) affected bone strength and metabolism. We tested the hypothesis that treatment with LP533401 could reverse CKD-induced bone loss in uremia.

Erythropoietin Intensifies the Proapoptotic Activity of LFM-A13 in Cells and in a Mouse Model of Colorectal Cancer.

The Bruton’s tyrosine kinase (BTK) inhibitor LFM-A13 has been widely employed as an antileukemic agent, but applications in solid cancer have been found recently. The compound promotes apoptosis, has an antiproliferative effect, and increases cancer cell sensitivity to chemotherapy drugs. We decided to assess the impact of the simultaneous use of erythropoietin (Epo) and LFM-A13 on signal transduction in colon DLD-1 and HT-29 cells, as well as in tumor xenografts.

RANKL/OPG system regulation by endogenous PTH and PTH1R/ATF4 axis in bone: Implications for bone accrual and strength in growing rats with mild uremia.

Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), and parathyroid hormone (PTH) play a central role in the regulation of bone turnover in chronic kidney disease (CKD), but their influence on bone mineral density (BMD) and strength remains unclear, particularly in children. We studied the clinical significance of OPG and RANKL in relation to PTH, femur weight, BMD, and bone biomechanical properties in growing rats after one month (CKD-1) and three months (CKD-3) of surgically-induced mild CKD. Gene expression of parathyroid hormone 1 receptor (PTH1R) and activating transcription factor 4 (ATF4), major regulators of anabolic PTH response in bone, was also determined.