Mitochondrial DNA and Inflammation Are Associated with Cerebral Vessel Remodeling and Early Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-ß-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)-the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease.

Recent Advances in Photochargeable Integrated and All-in-One Supercapacitor Devices.

Photoassisted energy storage systems, which enable both the conversion and storage of solar energy, have attracted attention in recent years. These systems, which started about 20 years ago with the individual production of dye-sensitized solar cells and capacitors and their integration, today allow more compact and cost-effective designs using dual-acting electrodes. Solar-assisted batterylike or hybrid supercapacitors have also shown promise with their high energy densities. This review summarizes all of these device designs and conveys the cutting-edge studies in this field. Besides, this review aims to emphasize the effects of point, extrinsic, intrinsic, and 2D-planar defects on the performance of photoassisted energy storage systems since it is known that defect structures, as well as electrical, optical, and surface properties, affect the device performance. Here, it is also targeted to draw attention to how critical the design, material selection, and material properties are for these new-generation energy conversion and storage devices, which have a high potential to see commercial examples quickly and to be recognized by more readers.

Design of smart nanoparticles for the electrochemical detection of 3,4-methylenedioxymethamphetamine to allow in field screening by law enforcement officers.

A portable and highly sensitive sensor was designed for the specific detection of 3,4-methyl-enedioxy-methamphetamine (MDMA), in a range of field-testing situations. The sensor can detect MDMA in street samples, even when other controlled substances drugs, or adulterants are present. In this work, we report for the first time a sensor using electroactive molecularly imprinted polymer nanoparticles computationally designed to recognize MDMA and then produced using solid phase synthesis. A composite comprising chitosan, reduced graphene oxide, and molecularly imprinted polymer nanoparticles synthesized for MDMA for the first time was immobilized on screen-printed carbon electrodes. The sensors displayed a satisfactory sensitivity (106.8 nA × µM-1 ), limit of detection (1.6 nM; 0.31 ng/mL), and recoveries (92-99%). The accuracy of the results was confirmed through validation using Ultra-High Performance Liquid Chromatography coupled with tandem Mass Spectrometry (UPLC-MS/MS). This technology could be used in forensic analysis and make it possible to selectively detect MDMA in street samples.

Mitochondrial DNA Changes in Blood and Urine Display a Specific Signature in Relation to Inflammation in Normoalbuminuric Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients.

Mitochondrial dysfunction is an important mechanism contributing to the development and progression of diabetic kidney disease (DKD). Mitochondrial DNA (mtDNA) levels in blood and urine were evaluated in relation to podocyte injury and proximal tubule (PT) dysfunction, as well as to a specific inflammatory response in normoalbuminuric DKD. A total of 150 type 2 diabetes mellitus (DM) patients (52 normoalbuminuric, 48 microalbuminuric, and 50 macroalbuminuric ones, respectively) and 30 healthy controls were assessed concerning the urinary albumin/creatinine ratio (UACR), biomarkers of podocyte damage (synaptopodin and podocalyxin), PT dysfunction (kidney injury molecule-1 (KIM-1) and N-acetyl-ß-(D)-glucosaminidase (NAG)), and inflammation (serum and urinary interleukins (IL-17A, IL-18, and IL-10)). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine via qRT-PCR. MtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies via analysis of the CYTB/B2M and ND2/B2M ratio. Multivariable regression analysis provided models in which serum mtDNA directly correlated with IL-10 and indirectly correlated with UACR, IL-17A, and KIM-1 (R2 = 0.626; p < 0.0001). Urinary mtDNA directly correlated with UACR, podocalyxin, IL-18, and NAG, and negatively correlated with eGFR and IL-10 (R2 = 0.631; p < 0.0001). Mitochondrial DNA changes in serum and urine display a specific signature in relation to inflammation both at the podocyte and tubular levels in normoalbuminuric type 2 DM patients.

Untargeted Metabolomics by Ultra-High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometry Analysis Identifies a Specific Metabolomic Profile in Patients with Early Chronic Kidney Disease.

Chronic kidney disease (CKD) has emerged as one of the most progressive diseases with increased mortality and morbidity. Metabolomics offers new insights into CKD pathogenesis and the discovery of new biomarkers for the early diagnosis of CKD. The aim of this cross-sectional study was to assess metabolomic profiling of serum and urine samples obtained from CKD patients. Untargeted metabolomics followed by multivariate and univariate analysis of blood and urine samples from 88 patients with CKD, staged by estimated glomerular filtration rate (eGFR), and 20 healthy control subjects was performed using ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry. Serum levels of Oleoyl glycine, alpha-lipoic acid, Propylthiouracil, and L-cysteine correlated directly with eGFR. Negative correlations were observed between serum 5-Hydroxyindoleacetic acid, Phenylalanine, Pyridoxamine, Cysteinyl glycine, Propenoylcarnitine, Uridine, and All-trans retinoic acid levels and eGFR. In urine samples, the majority of molecules were increased in patients with advanced CKD as compared with early CKD patients and controls. Amino acids, antioxidants, uremic toxins, acylcarnitines, and tryptophane metabolites were found in all CKD stages. Their dual variations in serum and urine may explain their impact on both glomerular and tubular structures, even in the early stages of CKD. Patients with CKD display a specific metabolomic profile. Since this paper represents a pilot study, future research is needed to confirm our findings that metabolites can serve as indicators of early CKD.

Photoluminescence and Photocatalytic Properties of MWNTs Decorated with Fe-Doped ZnO Nanoparticles.

The present work reports the photoluminescence (PL) and photocatalytic properties of multi-walled carbon nanotubes (MWCNTs) decorated with Fe-doped ZnO nanoparticles. MWCNT:ZnO-Fe nanocomposite samples with weight ratios of 1:3, 1:5 and 1:10 were prepared using a facile synthesis method. The obtained crystalline phases were evidenced by X-ray diffraction (XRD). X-ray Photoelectron spectroscopy (XPS) revealed the presence of both 2+ and 3+ valence states of Fe ions in a ratio of approximately 0.5. The electron paramagnetic resonance EPR spectroscopy sustained the presence of Fe3+ ions in the ZnO lattice and evidenced oxygen vacancies. Transmission electron microscopy (TEM) images showed the attachment and distribution of Fe-doped ZnO nanoparticles along the nanotubes with a star-like shape. All of the samples exhibited absorption in the UV region, and the absorption edge was shifted toward a higher wavelength after the addition of MWCNT component. The photoluminescence emission spectra showed peaks in the UV and visible region. Visible emissions are a result of the presence of defects or impurity states in the material. All of the samples showed photocatalytic activity against the Rhodamine B (RhB) synthetic solution under UV irradiation. The best performance was obtained using the MWCNT:ZnO-Fe(1:5) nanocomposite samples, which exhibited a 96% degradation efficiency. The mechanism of photocatalytic activity was explained based on the reactive oxygen species generated by the nanocomposites under UV irradiation in correlation with the structural and optical information obtained in this study.

A simple approach for coffee-ring suppression yielding homogeneous drying patterns of ZnO and TiO2 nanoparticles.

Evaporation-induced self-assembly in colloidal droplets is a method for organising nanoparticles on substrates, with various resulting patterns. The coffee-ring pattern is among the most common ones, but its non-uniformity limits its applicability, which led to efforts for developing coffee-ring suppression strategies. Considering the wide applicability of ZnO and TiO2 nanoparticles, there is a high demand for practical means to deposit them as uniform films. Here, we present a simple approach for obtaining highly uniform thin films of ZnO and TiO2 nanoparticles by drop-coating in ambient conditions, without using surfactants or other surface chemistry modifications. Disc-like films were obtained via a restricted evaporation achieved by covering the droplets with a lid during drying, seconded by the relatively high sedimentation rate of these nanoparticles. To better understand the assembly mechanism, the influence of suspension concentration, type and temperature of the substrate, droplet volume, colloid type, and evaporation rate were studied. The method allows preparing disc-like nanoparticle films with a good control over their diameter and thickness, onto different kinds of substrates (glass, Si, polyethylene terephthalate, polystyrene). By fabricating both two-dimensional lattices and custom disc patterns we highlight the versatility of this drop-coating method and its potential for, e.g., automatized serial production processes.

Facile Preparation of PVDF/CoFe2O4-ZnO Hybrid Membranes for Water Depollution.

In this investigation, CoFe2O4-PVDF and CoFe2O4-ZnO-PVDF hybrid membranes were prepared using a modified phase inversion method in which a magnetic field was applied during the casting process to ensure a uniform distribution of nanomaterials on the membrane surface. Thus, better absorption of light and increased participation of nanoparticles in the photodegradation process is ensured. The influence of nanomaterials on the crystalline structure, surface morphology, and hydrophilicity properties of the PVDF membrane was investigated. The obtained results indicated that the hybrid membrane exhibited significant differences in its intrinsic properties due to the nanomaterials addition. The hydrophilicity properties of the PVDF membrane were improved by the presence of nanoparticles. The photocatalytic decomposition of aqueous Rhodamine B solution in the presence of the prepared membrane and under visible light irradiation was tested. The hybrid membrane containing CoFe2O4-ZnO on its surface exhibited a high removal rate.

Effects of Colchicine in a Rat Model of Diet-Induced Hyperlipidemia.

Inflammation and hyperlipidemia play an essential role in the pathophysiology of endothelial dysfunction as well as atherosclerotic plaque formation, progression and rupture. Colchicine has direct anti-inflammatory effects by inhibiting multiple inflammatory signaling pathways. The purpose of our study was to evaluate colchicine activity in an animal model of hyperlipidemia induced by diet. A total of 24 male rats (wild type, WT) were divided into three groups: group one fed with a basic diet (BD) (WT + BD, n = 8), group two fed with a high-fat diet (HFD) (WT + HFD, n = 8)), and group three which received HFD plus drug treatment (colchicine, 0.5 mg/kg, i.p., daily administration). Total cholesterol, LDL-, HDL-cholesterol and triglycerides were determined. In addition, plasma transaminases, inflammation of oxidative stress markers, were measured. Tissue samples were evaluated using hematoxylin-eosin and red oil stain. At the end of the study, rats presented increased serum lipid levels, high oxidative stress and pro-inflammatory markers. The aortic histopathological section revealed that HFD induced signs of endothelial dysfunction. Colchicine treatment significantly resolved and normalized these alterations. Moreover, colchicine did not influence NAFLD activity score but significantly increased ALT and AST levels, suggesting that colchicine amplified the hepatocellular injury produced by the diet. Colchicine reduces plasma lipid levels, oxidative stress and inflammation markers and leads to more favorable histopathologic vascular and cardiac results. However, the adverse effects of colchicine could represent an obstacle to its safe use.

Electrospun Nanosystems Based on PHBV and ZnO for Ecological Food Packaging.

The electrospun nanosystems containing poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and 1 wt% Fe doped ZnO nanoparticles (NPs) (with the content of dopant in the range of 0-1 wt% Fe) deposited onto polylactic acid (PLA) film were prepared for food packaging application. They were investigated by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), antimicrobial analysis, and X-ray photoelectron spectrometry (XPS) techniques. Migration studies conducted in acetic acid 3% (wt/wt) and ethanol 10% (v/v) food simulants as well as by the use of treated ashes with 3% HNO3 solution reveal that the migration of Zn and Fe falls into the specific limits imposed by the legislation in force. Results indicated that the PLA/PHBV/ZnO:Fex electrospun nanosystems exhibit excellent antibacterial activity against the Pseudomonas aeruginosa (ATCC-27853) due to the generation of a larger amount of perhydroxyl (˙OOH) radicals as assessed using electron paramagnetic resonance (EPR) spectroscopy coupled with a spin trapping method.

Pharmacological Effects of Methotrexate and Infliximab in a Rats Model of Diet-Induced Dyslipidemia and Beta-3 Overexpression on Endothelial Cells.

BACKGROUND: Hyperlipidemia and inflammation are critical components in the pathophysiology of endothelial disorder, which can lead to vascular complications. Our study aimed to evaluate the effects of immunomodulatory therapy (methotrexate and infliximab) in a diet-induced hyperlipidemia rat model. METHODS: Sprague-Dawley (wild type (WT), male, n = 32) rats were divided into four groups: one group fed with standard diet (SD), one group fed with high lipid diet (HLD), and two groups that received HLD and drug treatment (methotrexate (Mtx) or infliximab (Ifx)). In order to evaluate if modifications to the endothelial cells may influence the risk of vascular complications following hyperlipidemia or treatment reactivity, each group was doubled by a rats group that overexpressed beta-3 receptors on the endothelial cells (transgenic (TG-beta 3), male, n = 32). Serum lipid profile, liver enzymes, oxidative stress, and inflammation markers were determined. Histopathologic analysis of the liver and aorta was performed. RESULTS: After 9 weeks of HLD, rats exhibited significant pathologic serum lipid profiles, elevated oxidative stress, and pro-inflammatory markers. Additionally, the aortic histopathological analysis revealed aorta media-intima thickening (p < 0.05) in the transgenic group. Methotrexate and infliximab significantly decreased inflammation and oxidative stress parameters, but presented opposing effects on lipid profiles (methotrexate decreased, whereas infliximab increased the atherosclerosis index). Drug treatment decreased the aorta media-intima thickness (p < 0.05) only in transgenic rats. CONCLUSIONS: HLD was associated with hyperlipidemia, inflammation and oxidative stress. The overexpression of beta-3 receptors on endothelial cells increased aortic thickening in response to the HLD. Methotrexate and infliximab reduced oxidative stress and inflammation in all groups, but led to favorable histopathologic vascular results only in the transgenic groups.

6 Years of Breast Reconstruction in One Center - An Objective Analysis.

Background: Breast cancer represents the most common type of neoplasm in women around the world. Breast reconstruction following mastectomy has become a demanding procedure in the treatment of patients suffering from breast cancer. Their major role is to improve the quality of life of women, leading to better aesthetic outcomes. Based on each type of reconstruction, the complications following surgery and the duration of hospital stay, the financial implications slightly vary. Methods: Our study included 168 female patients who underwent immediate or delayed breast reconstruction after mastectomy. We assessed the clinical management of each of these cases and we evaluated the average final cost of the treatment after the reconstruction, focusing on the reconstructive method used, the complications that occurred and the number of days of hospitalization. Results: The total cost of care in breast reconstruction surgery depends on the type of reconstructive procedure used, which consequently affects the duration of hospitalization of the patients. The expenses also depend on the materials that are used: the type of implant/expander or the use of ADM. Costs were higher in patients who underwent breast reconstruction using a latissimus dorsi flap associated with an implant, in comparison to reconstruction using a free flap. Conclusions: Breast reconstruction represents a crucial process in the management of women who underwent mastectomies following cancer and presumes variable financial resources, depending on the chosen reconstructive method.

Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients.

Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

Clinical and Pathogenic Correlations Between SARS-CoV-2 Infection and Hemolytic Uremic Syndrome in Children.

Background The present paper examines the correlations between coronavirus disease (COVID-19) and hemolytic uremic syndrome (HUS) from a clinical and pathophysiological point of view. Method: We describe COVID-19 and HUS by outlining the similarities and differences, detailing each one's pathway into the body, explaining the consequences of the inflammatory response, mainly on multiple organ dysfunction, the foremost complication that can lead to death in both cases. Using reviews from specialized literature and guidelines, we had an approach based on critical interpretive synthesis. Nonetheless, the present article has certain limitations, mainly due to the short period from the emergence of the virus and the everincreasing body of research that have been shedding light each day. Discussion: Both COVID-19 and HUS require binding to a membrane receptor to trigger the pathophysiological mechanism. Despite the evident difference in tropism, both conditions develop with severe endothelial dysfunction, microangiopathy and important inflammatory response, responsible for MODS. The role of the coagulation pathway is more significant in COVID-19 but less in HUS. Excessive complement activation appears to be a determinant of severe prognosis in both diseases. Regarding COVID-19, children have a milder symptomatology than adults, but in some cases the paediatric inflammatory multisystem syndrome (PIMS) is described.

Urinary proteins detected using modern proteomics intervene in early type 2 diabetic kidney disease - a pilot study.

Aim: An advanced proteomics platform for protein biomarker discovery in diabetic chronic kidney disease (DKD) was developed, validated and implemented. Materials & methods: Three Type 2 diabetes mellitus patients and three control subjects were enrolled. Urinary peptides were extracted, samples were analyzed on a hybrid LTQ-Orbitrap Velos Pro instrument. Raw data were searched using the SEQUEST algorithm and integrated into Proteome Discoverer platform. Results & discussion: Unique peptide sequences, resulted sequence coverage, scoring of peptide spectrum matches were reported to albuminuria and databases. Five proteins that can be associated with early DKD were found: apolipoprotein AI, neutrophil gelatinase-associated lipocalin, cytidine deaminase, S100-A8 and hemoglobin subunit delta. Conclusion: Urinary proteome analysis could be used to evaluate mechanisms of pathogenesis of DKD.

Antibiotics in the environment: causes and consequences.

Antibiotics represent one of the main discoveries of the last century that changed the treatment of a large array of infections in a significant way. However, increased consumption has led to an exposure of bacterial communities and ecosystems to a large amount of antibiotic residues. This paper aims to provide a brief overview of the primary drivers associated with antibiotic occurrence in the environment. Furthermore, we attempted to summarize the behavior of antibiotic residues in the environment and the necessity of their detection and quantification. Also, we provide updated scientific and regulatory facts about environmental antibiotic discharge and environmental and human antibiotics risk assessment. We propose that environmental antibiotic contamination should be diminished beginning from regulating the causes of occurrence in the environment (such as antibiotic consumption) and ending with regulating antibiotic discharge and risk assessment. Some important intermediate steps are represented by the detection and quantification of the antibiotics and the characterization of their behavior in the environment, which could come to support future regulatory decisions.

Photocatalytic and Electrocatalytic Properties of NGr-ZnO Hybrid Materials.

N-doped graphene-ZnO hybrid materials with different N-doped graphene:ZnO wt% ratios (1:10; 1:20; 1:30) were prepared by a simple and inexpensive sol-gel method. The materials denoted NGr-ZnO-1 (1:10), NGr-ZnO-2 (1:20), and NGr-ZnO-3 (1:30) were investigated with advanced techniques and their morpho-structural, photocatalytic, and electrocatalytic properties were reported. Hence, pure N-doped graphene sample contains flakes with the size ranging from hundreds of nanometers to micrometers. In the case of all NGr-ZnO hybrid materials, the flakes appear heavily decorated with ZnO nanoparticles, having a cauliflower-like morphology. The X-ray powder diffraction (XRD) investigation of N-doped graphene sample revealed that it was formed by a mixture of graphene oxide, few-and multi-layer graphene. After the ZnO nanoparticles were attached to graphene, major diffraction peaks corresponding to crystalline planes of ZnO were seen. The qualitative and quantitative compositions of the samples were further evidenced by X-ray photoelectron spectroscopy (XPS). In addition, UV photoelectron spectroscopy (UPS) spectra allowed the determination of the ionization energy and valence band maxima. The energy band alignment of the hybrid materials was established by combining UV-Vis with UPS results. A high photocatalytic activity of NGr-ZnO samples against rhodamine B solution was observed. The associated reactive oxygen species (ROS) generation was monitored by electron paramagnetic resonance (EPR)-spin trapping technique. In accordance with bands alignment and identification of radical species, the photocatalytic mechanism was elucidated.

Antioxidant Effects of Walnut (Juglans regia L.) Kernel and Walnut Septum Extract in a D-Galactose-Induced Aging Model and in Naturally Aged Rats.

Antioxidant dietary intervention is considered a potential strategy in delaying age-related dysfunctions. In this study of 56 days, we assessed the antioxidant effects of walnut kernel (WK) and walnut septum extract (WSE) in a D-galactose (D-gal)-induced aging model and in a naturally aged rat model. Young Wistar rats, treated with D-gal (1200 mg/week), and old rats received daily WK or WSE added to the feed. After 8 weeks, blood, liver, and brain samples were collected and hematological, biochemical, oxidative stress biomarkers, histological, and immunohistochemical analyses were performed. Moreover, acetylcholinesterase activity was investigated in brain homogenates. The outcomes demonstrated significant improvement in cellular antioxidant activity and/or decrease of reactive oxygen species, advanced glycation end products, nitric oxide, malondialdehyde, or increase of glutathione after WK or WSE intake in both models. Additionally, WSE showed hypoglycemic effect, and both WK and WSE lowered acetylcholinesterase activity. Both diets could protect neurons against the induced senescence and could reverse the pathological conditions in the physiological aged brain. Thus, dietary supplementation with WK or WSE can maintain the liver and brain health and reduce the risk of age-related diseases, as well as delaying the onset of aging processes.

Interindividual Variability of Apixaban Plasma Concentrations: Influence of Clinical and Genetic Factors in a Real-Life Cohort of Atrial Fibrillation Patients.

(1) Background: Prescribing apixaban for stroke prevention has significantly increased in patients with non-valvular atrial fibrillation (NVAF). The ABCB1 genotype can influence apixaban absorption and bioavailability. The aim of the present study was to assess the factors that influence apixaban's plasma level and to establish if a certain relationship has clinical relevance. (2) Methods: Fifty-three NVAF patients were treated with 5 mg apixaban twice/day (70.0 years, range: 65-77, 60.4% men). Trough and peak plasma concentrations of apixaban were determined by liquid chromatography-tandem mass-spectrometry (LC-MS/MS), and ABCB1 genotyping was performed. (3) Results: Apixaban plasma concentrations varied considerably. They were higher in women than in men (311.2 ng/dL vs. 252.2 ng/dL; p = 0.05) and were lower in patients with heart failure (149.4 ng/dL vs. 304.5 ng/dL; p < 0.01). Creatinine clearance was inversely correlated with the apixaban plasma level (Spearman correlation: r = -0.365; p = 0.007 for trough concentrations). No statistically significant differences between the genotypic groups of ABCB1 rs1045642 and ABCB1 rs4148738 were found in the trough or peak apixaban plasma concentrations. (4) Conclusions: Pharmacokinetic parameters are influenced by several clinical factors of which renal function is the major determinant. Plasma concentrations measured in women had higher values than those measured in men, and heart failure was associated with decreased plasma levels of apixaban.

Pro-inflammatory cytokines are associated with podocyte damage and proximal tubular dysfunction in the early stage of diabetic kidney disease in type 2 diabetes mellitus patients.

AIMS: To evaluate if there is a link between inflammation (expressed by inflammatory cytokines) and the early stage of diabetic kidney disease (DKD), as shown by markers of podocyte damage and proximal tubular (PT) dysfunction. METHODS: In this study were enrolled 117 type 2 DM patients (36-normoalbuminuria, 42-microalbuminuria, 39- macroalbuminuria), and 11 healthy subjects. Serum and urinary IL-1 alpha, IL-8, IL-18, urinary albumin:creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (podocalyxin, synaptopodin, nephrin) and of PT dysfunction (KIM-1, NAG) were assessed. RESULTS: In multivariable regression urinary Il-1 alpha correlated positively with podocalyxin and NAG (p < 0.0001, R2= 0.57); urinary IL-8 correlated directly with synaptopodin, NAG, nephrin, and KIM-1 (p < 0.0001, R2 = 0.67); urinary IL-18 correlated directly with synaptopodin, NAG, and nephrin (p < 0.0001, R2 = 0.59). Serum IL-1 alpha correlated positively with nephrin, synaptopodin, NAG (P < 0.0001, R2 = 0.68); serum IL-8 correlated directly with synaptopodin and NAG (p < 0.0001, R2 = 0.66); serum IL-18 correlated directly with NAG, KIM-1, and podocalyxin (p < 0.0001, R2=0.647). CONCLUSIONS: Pro-inflammatory interleukins are associated with podocyte injury and PT dysfunction in early DKD. These could exert a key role in the pathogenesis of early DKD, before the development of albuminuria.