Search Results (16,453)

Beyond their established hypoglycemic, cardioprotective, and nephroprotective properties, sodium–glucose cotransporters 2 (SGLT2) inhibitors exert other pleiotropic actions on blood pressure levels, body weight, and lipid metabolism. Blood pressure (BP) reduction varies based on the background history, including an effect on systolic, diastolic BP, and 24 h BP measurements. The reduction in body weight between 1 and 2 kg for the first months is caused by a reduction in visceral and subcutaneous fat due to glycosuria and loss of calories. Regarding lipid metabolism, a reduction in triglycerides and an increase in total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) have been reported, although these alterations are small and could provide additional cardiovascular protection. Various pathophysiologic mechanisms have been proposed to explain the above-mentioned pleiotropic actions of SGLT2 inhibitors. Natriuresis, osmotic diuresis, body weight reduction, amelioration of endothelial dysfunction and arterial stiffness, sympathetic tone decrease, and uric acid reduction are among those that have been suggested for BP reduction. Apart from glycosuria and calorie loss, other mechanisms seem to contribute to body weight reduction, such as the beiging of white adipose tissue, while the mechanisms involved in lipid metabolism alterations have not been clearly determined. Full article

Obesity promotes metabolic diseases such as type 2 diabetes and cardiovascular disease. PKCδI is a serine/threonine kinase which regulates cell growth, differentiation, and survival. Caspase-3 cleavage of PKCδI releases the C-terminal catalytic fragment (PKCδI_C), which promotes inflammation and apoptosis. We previously demonstrated an increase in PKCδI_C in human obese adipose tissue (AT) and adipocytes. Subsequently, we designed a small molecule drug called NP627 and demonstrated that NP627 specifically inhibited the release of PKCδI_C in vitro. Here, we evaluate the in vivo safety and efficacy of NP627 in a diet-induced obese (DIO) mouse model. The results demonstrate that NP627 treatment in DIO mice increased glucose uptake and inhibited the cleavage of PKCδI_C in the AT as well as in the kidney, spleen, and liver. Next, RNAseq analysis was performed on the AT from the NP627-treated DIO mice. The results show increases in ADIPOQ and CIDEC, upregulation of AMPK, PI3K-AKT, and insulin signaling pathways, while inflammatory pathways were decreased post-NP627 administration. Further, levels of lncRNAs associated with metabolic pathways were affected by NP627 treatment. In conclusion, the study demonstrates that NP627, a small-molecule inhibitor of PKCδI activity, is not toxic and that it improves the metabolic function of DIO mice in vivo. Full article

Purpose: The aim of the present study was to investigate the impact of medication reconciliation by pharmacists at both admission and discharge in hospitalized patients with different kidney diseases. Methods: A prospective study was performed in adult nephrology wards of a teaching referral hospital in Iran from September 2020 to March 2021. All patients hospitalized in the nephrology ward for at least 1 day who received the minimum of one medication during their ward stay within the study period were considered eligible. Medication reconciliation was performed by taking a best-possible medication history from eligible patients during the first 24 h of ward admission. Medications were evaluated for possible intentional as well as unintentional discrepancies. Results: Here, 178 patients at admission and 134 patients at discharge were included. The mean numbers of unintentional drug discrepancies for each patient at admission and discharge were 6.13 ± 4.13 and 1.63 ± 1.94, respectively. The mean ± SD numbers of prescribed medications for patients before ward admission detected by the nurse/physician and pharmacist were 6.06 ± 3.53 and 9.22 ± 4.71, respectively (p = 0.0001). The number of unintentional discrepancies at admission and discharge had a significant correlation with the number of drugs used and underlying diseases. The number of unintentional discrepancies at admission was also correlated with patients’ age. The number of comorbidities was significantly associated with the number of unintentional medication discrepancies at both admission and discharge. At the time of ward discharge, all patients were given medication consultations. Conclusions: The rate of reconciliation errors was high in the adult nephrology ward. The active contribution of pharmacists in the process of medication reconciliation can be significantly effective in identifying these errors. Full article

Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO’s aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe–TMAO pathway. Full article

The present work proposes a method for the synthesis of a nanoparticle with a superparamagnetic Fe₃O₄ core coated with SiO₂-NH₂ by ultrasound-assisted coprecipitation. Additionally, the nanoparticle is functionalized with a microinflammation biomarker peptide, and its effects on the viability of monkey kidney endothelial cells and the Vero cell line were evaluated. The main physicochemical properties of the nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray Photoemission Spectroscopy (XPS), a vibrating sample magnetometer (VSM), a field emission scanning electron, Scanning Electron Microscopy (SEM), and High-Resolution Transmission Electron Microscopy (HR-TEM). The results showed that the nanoparticles are spherical, with sizes smaller than 10 nm, with high thermal stability and superparamagnetic properties. They also demonstrated cell viability rates exceeding 85% through Magnetic Resonance Imaging (MRI). The results indicate the potential of these nanoparticles to be used as a contrast agent in magnetic resonance to detect mild brain lesions. Full article

This study aimed to explore the health impacts, mechanisms of toxicity, and key gene biomarkers of a mixture of the most prominent perfluoroalkyl/polyfluoroalkyl substances (PFAS) through in silico ADMET and toxicogenomic analysis. The following databases and tools were used: AdmetSAR (2.0), ADMETlab (2.0), Comparative Toxicogenomic Database, ToppGene Suite portal, Metascape (3.5), GeneMANIA server, and CytoHubba and CytoNCA Cytoscape (3.10.3) plug-ins. ADMET analysis showed that PFAS compounds pose risks of organ-specific toxicity, prolonged retention, and metabolic disruptions. Forty mutual genes were identified for all the tested PFAS. The mutual gene set was linked to disruption of lipid metabolism, particularly through nuclear receptors. The most important gene clusters identified were nuclear receptor signaling and PPAR signaling pathways, with kidney and liver diseases, diabetes, and obesity as the most significant related diseases. Phenotype data showed that PFAS compounds impact cell death, growth, inflammation, steroid biosynthesis, and thyroid hormone metabolism. Gene network analysis revealed that 52% of the 40 mutual genes showed co-expression, with co-localization as the next major interaction (18.23%). Eight key genes were extracted from the network: EHHADH, APOA2, MBL2, SULT2A1, FABP1, PPARA, PCK2, and PLIN2. These results highlight the need for further research to fully understand the health risks of PFAS mixtures. Full article

The gut dysbiosis present in chronic kidney disease (CKD) has been associated with anemia. Factors such as the accumulation of gut-derived uremic toxins, increased gut barrier permeability-induced inflammation, and a reduced intestinal production of short-chain fatty acids (SCFAs), all associated with changes in the intestinal microbiota composition in CKD, may lead to the development or worsening of anemia in renal patients. Understanding and addressing these mechanisms related to gut dysbiosis in CKD patients can help to delay the development of anemia and improve its control in this population. One approach is to avoid or reduce the use of drugs linked to gut dysbiosis in CKD, such as phosphate binders, oral iron supplementation, antibiotics, and others, unless they are indispensable. Another approach involves introducing dietary changes that promote a healthier microbiota and/or using prebiotics, probiotics, or symbiotics to improve gut dysbiosis in this setting. These measures can increase the presence of SCFA-producing saccharolytic bacteria and reduce proteolytic bacteria, thereby lowering the production of gut-derived uremic toxins and inflammation. By ameliorating CKD-related gut dysbiosis, these strategies can also improve the control of renal anemia and enhance the responsiveness to erythropoiesis-stimulating agents (ESAs) in ESA-resistant patients. In this review, we have explored the relationship between gut dysbiosis in CKD and renal anemia and propose feasible solutions, both those already known and potential future treatments. Full article

Mentha longifolia (L.) L., also known as wild mint, is a perennial herbaceous plant that belongs to the Lamiaceae family. This study aimed to investigate the effects of essential oil of M. longifolia (MLEO) on oxidative stress and inflammatory responses in the liver and kidneys in the context of drug-induced liver injury caused by the anti-TB drugs rifampicin, isoniazid, and pyrazinamide (INH-RIF-PZA). The chemical composition of MLEO was characterized using GC/MS analysis, which revealed the presence of pulegone, trans-p-menthan-3-one, piperitenone, and β-caryophyllene as its major volatile constituents. An INH/RIF/PZA mixture was administered to Wistar rats for 30 days, and silymarin was administered as a standard drug. MLEO was administered p.o. at doses of 50 mg and 100 mg/kg b.w. Both doses of the MLEO therapy effectively regulated all biochemical indicators of hepatic impairment and reduced the damage caused by the INH/RIF/PZA mixture. It may be deduced that MLEO has the ability to protect organs against INH/RIF/PZA-induced damage and could potentially be a valuable natural remedy for treating anti-TB-induced liver and kidney injuries. Full article

The classical function of the mineralocorticoid receptor (MR) is to maintain electrolytic homeostasis and control extracellular volume and blood pressure. The MR is expressed in the central nervous system (CNS) and is involved in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis as well as sleep physiology, playing a role in the non-rapid eye movement (NREM) phase of sleep. Some patients with psychiatric disorders have very poor sleep quality, and a relationship between MR dysregulation and this disorder has been found in them. In addition, the MR is involved in the regulation of the renal peripheral clock. One of the most common comorbidities observed in patients with chronic kidney disease (CKD) is poor sleep quality. Patients with CKD experience sleep disturbances, including reduced sleep duration, sleep fragmentation, and insomnia. To date, no studies have specifically investigated the relationship between MR activation and CKD-associated sleep disturbances. However, in this review, we analyzed the environment that occurs in CKD and proposed two MR-related mechanisms that may be responsible for these sleep disturbances: the circadian clock disruption and the high levels of MR agonist observed in CKD. Full article

Twelve clinically healthy and sexually mature New Zealand White rabbits were studied. The non-contrast imaging included T1-weighted and T2-weighted spin-echo and gradient-echo sequences in the transverse, sagittal and dorsal planes. Transverse MRI (T2-weighted image) through L1 demonstrated only the right kidney. The transverse T2-weighted image through L2 showed both kidneys. The cranial part of the urinary bladder on T1-weighted transverse scans through L4 was flexed to the left. The T2-weighted sagittal image 30 mm to the right of the median plane showed the right kidney, the right ureter and the urinary bladder. The T2-weighted sagittal image 30 mm to the left of the median plane showed part of the left kidney, the left ureter and the urinary bladder. The T2-weighted sagittal image 45 mm to the left of the median plane presented the lateral part of the left kidney. The dorsal MRI image (T2-weighted sequence) through the horizontal plane 30 mm ventral to the spine demonstrated the whole organs. These data will be useful in imaging anatomy and diagnostic studies of various pathologies of the excretory system in rabbits and other mammalian species. Full article

Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), contributing to significant morbidity, mortality, and rising healthcare costs. In this review article, we explore the role of epigenetic mechanisms in HN progression and their potential therapeutic implications. We begin by examining key epigenetic modifications—DNA methylation, histone modifications, and non-coding RNAs—observed in kidney disease. Next, we discuss the underlying pathophysiology of HN and highlight current in vitro and in vivo models used to study the condition. Finally, we compare various types of HN-induced renal injury and their associated epigenetic mechanisms with those observed in other kidney injury models, drawing inferences on potential epigenetic therapies for HN. The information gathered in this work indicate that epigenetic mechanisms can drive the progression of HN by regulating key molecular signaling pathways involved in renal damage and fibrosis. The limitations of Renin–Angiotensin–Aldosterone System (RAAS) inhibitors underscore the need for alternative treatments targeting epigenetic pathways. This review emphasizes the importance of further research into the epigenetic regulation of HN to develop more effective therapies and preventive strategies. Identifying novel epigenetic markers could provide new therapeutic opportunities for managing CKD and reducing the burden of ESRD. Full article

Danofloxacin is a fluoroquinolone antibiotic approved for use in fish. It can be used for bacterial infections in fish of all body sizes. However, physiological differences in fish depending on size may change the pharmacokinetics of danofloxacin and therefore its therapeutic efficacy. In this study, the change in the pharmacokinetics of danofloxacin in rainbow trout of various body sizes was revealed for the first time. The objective of this investigation was to compare the plasma and tissue pharmacokinetics of danofloxacin in rainbow trout of different body sizes. The study was conducted at 14 ± 0.5 °C in fish of small, medium, and large body size and danofloxacin was administered orally at a dose of 10 mg/kg. Concentrations of this antimicrobial in tissues and plasma were quantified by high performance liquid chromatography with ultraviolet detector. The plasma elimination half-life (t_1/2ʎz), volume of distribution (V_darea/F), total clearance (CL/F), peak concentration (C_max), and area under the plasma concentration–time curve (AUC_0–last) were 27.42 h, 4.65 L/kg, 0.12 L/h/kg, 2.53 µg/mL, and 82.46 h·µg/mL, respectively. Plasma t_1/2ʎz, AUC_0–last and C_max increased concomitantly with trout growth, whereas CL/F and V_darea/F decreased. Concentrations in liver, kidney, and muscle tissues were higher than in plasma. C_max and AUC_0–last were significantly higher in large sizes compared to small and medium sizes in all tissues. The scaling factor in small, medium, and large fish was 1.0 for bacteria with MIC thresholds of 0.57, 0.79, and 1.01 µg/mL, respectively. These results show that therapeutic efficacy increases with body size. However, since increases in danofloxacin concentration in tissues of large fish may affect withdrawal time, attention should be paid to the risk of tissue residue. Full article

(1) Background: donor-derived circulating free DNA (dd-cfDNA), an innovative biomarker with great potential for the early identification and prevention of graft damage. (2) Methods: Samples were collected prospectively and the study was performed retrospectively to analyze dd-cfDNA plasma levels in 30 kidney transplant patients during their post-transplant follow-up (15 days, 3, 6, and 9 months), to determine if the result could be of interest in the identification of possible adverse events, especially rejection. The aim was to verify whether the data on sensitivity, specificity, NPV, and PPV compare with reference values and creatinine values. (3) Results: We observed levels of dd cfDNA > 1% in six of nine patients with active rejection (ABMR or TCMR) and elevated values (>0.5%) in two other patients in this rejection group. Our results show low values of sensitivity = 50%, specificity = 61.11%, rejection NPV = 64.71%, and rejection PPV = 46.13% of the technique compared to reference values previously published. With respect to creatinine, only for TCRM, we observed better results for dd-cfDNA in these parameters than in creatinine. Also, our data suggest that dd-cfDNA could help to differentiate those patients with dnDSAs that are going to through rejection better than creatinine, specially at 15 d post transplant. In this study, this appears to have no positive predictive value for borderline rejection (BR) or TCMR IA. (4) Conclusions: plasma levels of dd-cfDNA could be considered an additional or alternative biomarker for graft rejection monitoring in early post-kidney transplant up to several months before its clinical presentation, especially for patients with suspected TCMR or ABMR. Full article

Sepsis-associated acute kidney injury (SA-AKI) presents a severe challenge in the elderly due to increasing incidence, high mortality, and the lack of specific effective treatments. Exploring novel and secure preventive and/or therapeutic approaches is critical and urgent. Berberine (BBR), an isoquinoline alkaloid with anti-inflammatory, antioxidant, and immunomodulatory properties, has shown beneficial effects in various kidney diseases. This study examined whether BBR could protect against SA-AKI in aged rats. Sepsis was induced in 26-month-old male Wistar rats by cecal ligation and puncture (CLP), either with or without BBR pretreatment. CLP induction led to SA-AKI, as indicated by elevated serum levels of malondialdehyde, tumor necrosis factor-alpha, urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL), along with histopathological features of kidney damage. Key indicators of kidney oxidative stress, mitochondrial dysfunction, apoptosis, and activations of the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling, including the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome pathway, were also elevated following CLP induction. BBR pretreatment substantially mitigated these adverse effects, suggesting that it protects against SA-AKI in aged rats by reducing oxidative stress, preserving mitochondrial integrity, and inhibiting key inflammatory pathways. These findings highlight the potential of BBR as a therapeutic agent for managing SA-AKI in elderly populations. Full article

Vitamin D insufficiency and deficiency are highly prevalent in patients with chronic kidney disease (CKD), and their pharmacokinetics are not well described. The primary study objective was to develop a population pharmacokinetic model of oral cholecalciferol (VitD₃) and its three major metabolites, 25-hydroxyvitamin D₃ (25D₃), 1,25-dihydroxyvitamin D₃ (1,25D₃), and 24,25-dihydroxyvitamin D₃ (24,25D₃), in CKD patients with vitamin D insufficiency and deficiency. CKD subjects (n = 29) were administered one dose of oral VitD₃ (5000 I.U.), and nonlinear mixed effects modeling was used to describe the pharmacokinetics of VitD₃ and its metabolites. The simultaneous fit of a two-compartment model for VitD₃ and a one-compartment model for each metabolite represented the observed data. A proportional error model explained the residual variability for each compound. No assessed covariate significantly affected the pharmacokinetics of VitD₃ and metabolites. Visual predictive plots demonstrated the adequate fit of the pharmacokinetic data of VitD₃ and metabolites. This is the first reported population pharmacokinetic modeling of VitD₃ and metabolites and has the potential to inform targeted dose individualization strategies for therapy in the CKD population. Based on the simulation, doses of 600 International Unit (I.U.)/day to 1000 I.U./day for 6 months are recommended to obtain the target 25D₃ concentration of between 30 and 60 ng/mL. These simulation findings could potentially contribute to the development of personalized dosage regimens for vitamin D treatment in patients with CKD. Full article