N-acetyl-β-D-glucosaminidase Research Articles

Tachycardia and acute kidney injury among critically ill patients with sepsis: a prospective observational study.

Tachycardia caused by sympathetic overactivity impairs myocardial function and raises septic patient mortality. This study examined whether tachycardia is associated with acute kidney injury (AKI) period-prevalence among critically ill patients with and without sepsis. In 328 patients (119 sepsis and 209 non-sepsis) admitted to our intensive care unit (ICU), we assessed heart rate at ICU admission, plasma neutrophil gelatinase-associated lipocalin (NGAL) and N-terminal pro-B-type natriuretic peptide, and urinary L-type fatty acid-binding protein and N-acetyl-β-D-glucosaminidase (NAG) at 0 and 48 hours after admission. Tachycardia was defined as a heart rate of above 100 beats/min. Tachycardia was independently correlated with AKI prevalence during the first week after ICU admission in the septic patients, but not in the non-septic patients. A dose-dependent increase in AKI period-prevalence was observed across ascending heart rate ranges. Furthermore, we discovered a dose-dependent increase of renal biomarker-positive patients regarding plasma NGAL and urinary NAG over increasing heart rate ranges 48 hours after admission. The findings revealed an independent relationship between tachycardia and AKI prevalence during the first week of ICU in septic patients. Heart rate was found to have a dose-dependent effect on AKI prevalence and renal insult monitored by biomarkers.

#1831 Circulating MiRNA 195-5p may be associated with early renal impairment in patients with prediabetes

Abstract Background and Aims Type 2 diabetes mellitus (DM) is one of the leading causes of chronic kidney disease worldwide. However, there are few data concerning early kidney impairment in prediabetes patients. The aim of the study was to demonstrate early kidney damage in patients with prediabetes by assessing proximal tubule (PT) dysfunction, podocytes injury, and miRNA expression. Method A cohort of 192 individuals were analysed and divided such as follows: 52-normoalbuminuria-, 48-microalbuminuria-, and 50-macroalbuminuria type 2 DM patients, respectively; 12 patients-prediabetes and 30-healthy controls. The miRNA profile was assessed by real-time PCR, while PT dysfunction biomarker, N-acetyl-β-D-glucosaminidase (NAG), and podocyte injury biomarker, podocalyxin, were assessed by ELISA technique. The study was conducted in two distinct stages. In the first part of the study was detected a particular miRNAs profile in serum in patients with prediabetes; subsequently, the expression of the most relevant miRNA in patients with prediabetes was identified. Results i) in prediabetes patients, serum miRNA195-5p was 2.69 fold change as compared to the control group and correlated with NAG (p<0.05) and podocalyxin (p<0.03); ii) in type 2 DM patients, the expression of serum miRNA195-5p was higher and correlated with NAG (p<0.05), podocalyxin (p<0.04), urinary albumin: creatinine ratio (p<0.001) and with eGFR (p<0.001); iii) urinary NAG and urinary podocalyxin were higher in prediabetes patients and type 2 DM patients, even in the normoalbuminuria stage, as compared to controls (p<0.04; p<0.001). Conclusion A panel of molecular biomarkers, such as miRNAs, remain useful tools for the early diagnosis of renal involvement in the course of type 2 DM. MiRNA 195-5p may be associated with PT dysfunction and podocyte damage, and could predict renal dysfunction in both prediabetes and early diabetic kidney disease in type 2 DM patients.

#1554 The association between gut-derived metabolites and biomarkers of renal and cerebro-vascular damage in type 2 diabetes mellitus patients

Abstract Background and Aims Due to its numerous complications, type 2 diabetes mellitus (T2DM) has a major impact on the global economic burden and overall mortality. This condition modifies the metabolic microenvironment in targeted organs, such as the kidney and the brain, by its hyperglycemic nature. Gut microbiota seems to have significant interference with the renal-cerebral axis, especially in a dysbiosis state. The aim of the study was to quantify gut derived metabolites by metabolomic techniques and to evaluate their association with markers of endothelial, podocyte and proximal tubule damage and with cerebro-vascular hemodynamic indices. Method The metabolomic profiling was realized on serum and urine samples originated from 90 T2DM patients, divided into three subgroups, such as the following: 30 normal to mildly-, 30 moderately-, and 30 severely increased albuminuria, respectively, and 20 healthy subjects. The samples were examined by using untargeted and targeted ultra-high performance liquid chromatography coupled with electrospray-ionization quadroupole time-of-flight mass spectrometry (UHPLC-QTOF-ESI+-MS), in order to obtain the metabolic profile. The markers of renal damage such as synaptopodin (SP), podocalyxin (PD), N-acetyl-β-D-glucosaminidase (NAG), kidney injury molecule 1 (KIM-1), monocyte chemotactic protein 1 (MCP-1), and intercellular adhesion molecule 1 (ICAM-1) were assessed by ELISA technique. The hemodynamic cerebro-vascular indices were obtained by high resolution Doppler ultrasound of common carotid arteries (CCAs), internal carotid arteries (ICAs), and middle cerebral arteries (MCAs), bilaterally. The correlations between the metabolites, the markers of renal damage, and neurosonological indices were realized by univariable and multivariable linear regression analyses. Results UHPLC-QTOF-ESI+-MS targeted analysis and subsequent statistical assessments revealed a subset of metabolites with a specific pattern for the normal to mildly increased albuminuria subgroup. The metabolites identified as significant were, in serum: arginine (sArg), hippuric acid (sHA), indoxyl sulfate (sIS), butenoylcarnitine (sBCA), sorbitol (sSorb); and in urine, arginine (uArg), butenoylcarnitine (uBCA), indoxyl sulfate (uIS) and p-cresyl sulfate (uPCS). The univariable linear regression analysis revealed that sArg correlated positively with the breath-holding index (BHI) and negatively with intima media thickness (IMT) in ACI, MCP-1 and ICAM-1; sIS, sSorb, and sBCA correlated inversely with these parametes. The multivariable linear regression analysis displayed the specific correlations between metabolites, markers of endothelial dysfunction, and neurosonological indices, such as follows: sArg correlated with IMT and ICAM-1; sIS followed a predictive pattern along with resistance index (RI) in ACIs and ICAM-1; sBCA correlated with IMT and MCP-1 and sSorb correlated with ICAM-1 and BHI. The urine metabolites were correlated with markers of podocyte and proximal tubule dysfunction: uIS and uBCA were correlated with PD and urinary albumin to-creatinin ratio (uACR), and uPCR correlated with KIM-1 and uACR. Conclusion This study revealed a set of metabolites potentially derived from the intestinal microflora which may act as biomarkers for the early detection of both CMA and DKD in T2DM patients. SArg, sIS and, sBCA are indicators of renal endothelial dysfunction. Moreover, sArg and sIS reflect incipient common and internal carotid artery atherosclerosis, suggesting vascular remodeling at these levels. SSorb correlated with BHI, indicating blood-brain barrier dysfunction and CMA development. In urine, uBCA and uIS are indicators of podocytopathy, whereas uPCS is associated with proximal tubule damage in incipient DKD.

Complex interplay of heavy metals and renal injury: New perspectives from longitudinal epidemiological evidence

BackgroundEpidemiological studies have reported associations between heavy metals and renal function. However, longitudinal studies are required to further validate these associations and explore the interactive effects of heavy metals on renal function and their directional influence. MethodThis study, conducted in Northeast China from 2016 to 2021, included a four-time repeated measures design involving 384 participants (1536 observations). Urinary concentrations of chromium (Cr), cadmium (Cd), manganese (Mn), and lead (Pb) were measured, along with renal biomarkers including urinary microalbumin (umAlb), urinary albumin-to-creatinine ratio (UACR), N-acetyl-β-D-glucosaminidase (NAG), and β2-microglobulin (β2-MG) levels. Estimated glomerular filtration rate (eGFR) was calculated. A Linear Mixed Effects Model (LME) examined the association between individual metal exposure and renal biomarkers. Subsequently, Quantile g-computation and Bayesian Kernel Machine Regression (BKMR) models assessed the overall effects of heavy metal mixtures. Marginal Effect models examined the directional impact of metal interactions in the BKMR on renal function. ResultResults indicate significant impacts of individual and combined exposures of Cr, Cd, Pb, and Mn on renal biomarkers. Metal interactions in the BKMR model were observed, with synergistic effects of Cd-Cr on NAG, umAlb, UACR; Cd-Pb on NAG, UACR; Pb-Cr on umAlb, UACR, eGFR-MDRD, eGFR-EPI; and an antagonistic effect of Mn-Pb-Cr on UACR. ConclusionBoth individual and combined exposures to heavy metals are associated with renal biomarkers, with significant synergistic interactions leading to renal damage. Our findings elucidate potential interactions among these metals, offering valuable insights into the mechanisms linking multiple metal exposures to renal injury.

Environmental risk score of multiple pollutants for kidney damage among residents in vulnerable areas by occupational chemical exposure in Korea

This study aimed to develop an environmental risk score (ERS) of multiple pollutants (MP) causing kidney damage (KD) in Korean residents near abandoned metal mines or smelters and evaluate the association between ERS and KD by a history of occupational chemical exposure (OCE). Exposure to MP, consisting of nine metals, four polycyclic aromatic hydrocarbons, and four volatile organic compounds, was measured as urinary metabolites. The study participants were recruited from the Forensic Research via Omics Markers (FROM) study (n = 256). Beta-2-microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR) were used as biomarkers of KD. Bayesian kernel machine regression (BKMR) was selected as the optimal ERS model with the best performance and stability of the predicted effect size among the elastic net, adaptive elastic net, weighted quantile sum regression, BKMR, Bayesian additive regression tree, and super learner model. Variable importance was estimated to evaluate the effects of metabolites on KD. When stratified with the history of OCE after adjusting for several confounding factors, the risks for KD were higher in the OCE group than those in the non-OCE group; the odds ratio (OR; 95% CI) for ERS in non-OCE and OCE groups were 2.97 (2.19, 4.02) and 6.43 (2.85, 14.5) for β2-MG, 1.37 (1.01, 1.86) and 4.16 (1.85, 9.39) for NAG, and 4.57 (3.37, 6.19) and 6.44 (2.85, 14.5) for eGFR, respectively. We found that the ERS stratified history of OCE was the most suitable for evaluating the association between MP and KD, and the risks were higher in the OCE group than those in the non-OCE group.

Organic fertilizer prepared by thermophilic aerobic fermentation technology enhanced soil humus and related soil enzyme activities

AbstractOrganic fertilizer (OF) prepared from chicken manure in a high‐temperature aerobic fermenter contains high levels of nitrogen, phosphorus and potassium. The effect of high‐nutrient OF substitution for chemical fertilizer (CF) on soil organic carbon stability is worth exploring. We used OF to replace CFs for supplying crops, and we set five OF replacement rates as 0, 25%, 50%, 75% and 100% in the black soil zone of Northeast China. We explored the variations in soil humus carbon contents, enzyme activities and nutrient contents (0–10 cm and 10–20 cm). Two‐way ANOVA results showed that interaction between soil depth and OF substitution significantly affected soil pH, total nitrogen, organic carbon, available potassium, water‐soluble carbon substance (WSSC) and activities of soil β‐galactosidase (β‐gal), N‐acetyl‐β‐D‐glucosaminidase (NAG) and cellobiohydrolase. The treatments of OF75 and OF100 increased soil pH, and the content of soil organic carbon, humic acid carbon (HAC), fulvic acid carbon (FAC), WSSC, total phosphorus, available phosphorus (AP), total potassium and available potassium was increased in OF75 and OF100 treatment. Treatments of OF75 and OF100 increased the tested soil enzyme activities except for oxidase activities of 0–10 cm soil layer. There was a positive correlation between HAC and AP contents, and a positive correlation between FAC and soil pH, total nitrogen and available potassium contents. The key influencing factors of soil FAC were the activities of NAG, α‐galactosidase and β‐gal. It can be concluded that OF substitution promoted soil humus carbon accumulation by affecting hydrolase activity related to carbon conversion.

Evaluation of Serum Human Kidney Injury Molecule-1 and N-Acetyl-β-D-Glucosaminidase as Early Markers of Kidney Injury in Patients with β-Thalassemia Major in Diyala Governorate

Thalassemia is a genetic disease identified by a defect in the production of one or more globin chains. This study was aimed at determining the possibility of using "serum kidney injury molecule-1 (KIM-1)" and "N-acetyl-β-D-glucosaminidase (NAG)" in the diagnosis of early renal damage in thalassemia patients. Serum biomarkers (CBC, urea, creatinine, KIM-1, and NAG) were determined in 45 patients with major thalassemia with an age range of 4-45 years who attended Baquba General Hospital. A significant increase in S.KIM-1 and S.NAG levels in patients compared with controls. The level of KIM was positively correlated with that of urea and creatinine in comparison with control. Also, the level of NAG was strongly positively correlated with the level of KIM-1 (p = 0.000) and had a moderately positive correlation with urea and creatinine (p = 0.000). According to ROC, KIM-1 had a sensitivity of 95.56% and a specificity of 88.89%, while NAG had a sensitivity of 100% and a specificity of 75.6%. This study concluded that S.KIM-1 and S.NAG are highly promising biomarkers for the detection of "acute kidney injury" in an early stage before elevated urea and creatinine in thalassemia patients.

Anchoring copper nanoclusters to Al2O3 microsphere for dual-mode analysis of N-acetyl-β-D-glucosaminidase and information encryption

Herein, we attempted to confine copper nanoclusters (CuNCs) with alumina (Al2O3) as the matrix (Al2O3@CuNCs), which effectively circumvented the drawbacks of CuNCs (such as weak photoluminescence and low quantum yield). Al2O3@CuNCs demonstrated sensitive response to p-nitrophenol, the catalytic product of N-acetyl-β-D-glucosaminidase (NAG) on account of the inner filter effect and dynamic quenching effect. In light of this, a novel assay was created to identify NAG, a critical indicator of diabetic nephropathy. Additionally, a portable and instrument-free sensing platform mainly consisting of a smartphone, a cuvette, a cuvette holder, a dark box and a 365 nm UV lamp was developed for the quantitative detection of NAG. The as-prepared material was also utilized in anti-counterfeiting and information encryption based on their excellent optical properties and sensitive response to the catalyzed product of NAG. This work advanced potential applications of CuNCs composites in the areas of portable, multi-mode biosensing, anti-counterfeiting and information encryption.

Effects of different maize residue managements on soil organic nitrogen cycling in different soil layers in northeast China

AbstractA field experiment was conducted in northeast China to examine the response of nitrogen cycling enzymes, that is, protease, N‐acetyl‐β‐D‐glucosaminidase (NAG), amidase, urease, and peptidase, as well soil organic nitrogen (SON) fractions and their relationships to RT (no maize residue application), NT (no tillage with maize residues placed on the surface), TT (plow maize residues into the soil at 0–35 cm depth in the first year, 0–20 cm in the second year, and 0–15 cm in the third year), and PT (plow maize residues into soil at 0–35 cm depth). The results have shown that NT significantly enhanced the activities of protease and NAG at 0–10 cm soil depth in comparison with other treatments. NT and TT significantly enhanced the activities of protease compared to RT and PT at 10–20 cm soil depth. TT significantly enhanced the activities of NAG in comparison with RT at 10–20 cm soil depth. TT and PT significantly enhanced the activities of NAG and peptidase compared to RT and NT at 20–35 cm soil depth. PT significantly increased the activities of protease in comparison with RT at 20–35 cm soil depth. NT, TT, and PT significantly enhanced the activities of peptidase compared to RT at 10–20 cm soil depth. NT significantly increased the concentration of hydrolyzable in comparison with other treatments at 0–10 cm soil depth. PT significantly enhanced the concentration of hydrolyzable and amino acid N compared to other treatments at 20–35 cm soil depth. Redundancy analysis showed that protease played a crucial role in the cycling of SON under RT and NT, whereas peptidase and NAG played a significant role in the cycling of SON under TT and PT, respectively. This study provided a comprehensive understanding of crop residue return methods for regulating soil N cycling.

Enzymological Studies of the Functional State of the Kidney Parenchyma in Children of the Younger Age Group with Congenital Megaureter

The objective: to determine the activity levels of total N-acetyl-β-D-glucosaminidase (NAG), its heat-stable isoenzyme NAG B and β-galactosidase (β-Gal) as enzymological criteria of the functional state of the kidney parenchyma, in particular its tubular part, in the urine of younger children age group with congenital megaureter (MU) depending on the degree of suppression of the urodynamics of the upper urinary tract (UUT). Materials and methods. Before reconstructive treatment 103 children aged 0.5 to 15 years with various clinical variants of congenital MU were examined. According to the degree of suppression of urodynamics of the UUT, the patients were divided into three groups: 1st group – 32 patients with I degree (initial degree), 2nd group – 41 children with II degree (medium one), 3rd group – 30 patients with III degree (expressed one). The control group included 25 practically healthy children. Patients were divided into two subgroups by age. Subgroup “a” included 29 patients aged from 0.5 to 3 years (average age – 1.4±0.5 years), of which 9 patients were examined in the 1st group, 13 persons – in the 2nd group, in 3d group – 7 patients. Subgroup “b” included 74 children aged 4 to 15 years (average age – 8.3±1.5 years). Enzymological activity of the morning portion of urine in patients was determined by the colorimetric method. Statistical processing of data was performed after analyzing the conformity of their distribution to normality. Results. It was established that the total activity of NAG and the activity of NAG B in the urine of all patients with congenital MU with the I degree of suppression of urodynamics of the UUT, regardless of age, probably exceeded the average data of similar indicators in the control group (p<0.05–0.001). In children with congenital MU with II degree suppression of urodynamics of the UUT, regardless of age, a similar trend of changes in the activity levels of all the studied enzymes was determined, compared to patients of the 1st group (р<0.02–0.001). The total activity of NAG, the activity of NAG B and β-Gal in the urine of patients with III degree of suppression of urodynamics of the UUT probably exceeded similar indicators compared to patients of the 2nd group regardless of the age (p<0.001). The results of the study showed that in patients with the I degree of suppression of urodynamics of the UUT between age groups there was no statistical probability of changes in the activity levels of the studied enzymes. In children under 3 years of age with III degree of inhibition of urodynamics of the UUT the levels of enzyme activity probably exceeded similar indicators in the group of patients of 3 years old and over (р<0.05–0.001). Enzyme activity levels of NAG and NAG B in the urine of patients under 3 years old with II degree of suppression of urodynamics of the UUT also statistically significantly exceeded the similar indicators of sick children over 3 years old (p<0.01). Conclusions. The intensity of the increase in the urinary activity of NAG, its thermostable isoenzyme NAG B and β-Gal in patients under 3 years old compared to the group of patients over the age of 3 years growths with an increase in the degree of suppression of the urodynamics of the UUT, which should be taken into account during treatment.

Individual and combined effects of earthworms and Sphingobacterium sp. on soil organic C, N forms and enzyme activities in non-contaminated and Cd-contaminated soil

Earthworms and Sphingobacterium sp. are known for their strong organic compound decomposition ability and wide distribution in soil. However, interactions of soil organic matter decomposition with soil properties and whether microbial species such as Sphingobacterium sp. could assist earthworms in carbon and nitrogen transformation in soil remain poorly understood. Earthworms (Eisenia fetida, Amynthas gracilis) and Sphingobacterium sp. were introduced in non-contaminated and cadmium-contaminated soils under controlled laboratory conditions for 20 days. We examined their individual or combined effects on carbon and nitrogen forms and related enzyme activities to assess their influence on soil C and N cycling. Individual Sphingobacterium sp. inoculation led to significantly decreased organic carbon (SOC) contents, reducing it by 16.5% in non-contaminated soil and by 3.77%, in Cd-contaminated soil. It resulted in an increased microbial biomass carbon (MBC) contents, reaching 1685 ± 292 mg·kg−1 in non-contaminated soil. Individual introductions of E. fetida and A. gracilis caused a decline in SOC content in non-contaminated soil, but increased significantly dissolved organic carbon (DOC) and alkali-hydrolysable nitrogen (AN) contents by 75.8%, 53.6% and 32.9%, 20.9%, respectively. In contrast, in Cd-contaminated soil, only the significant combined effects of earthworms and Sphingobacterium sp. were linked to significant increase in SOC contents, raising by 7.22% and 9.64% in E. fetida + Sphingobacterium sp. and A. gracilis + Sphingobacterium sp. treatments, respectively. In non-contaminate soil, the combined effects of earthworm and Sphingobacterium sp. further increased DOC and AN content by 212%, 134% and 31.3%, 25.4% in the treatments of E. fetida + Sphingobacterium sp. and A. gracilis + Sphingobacterium sp., respectively; the highest ratios of DOC to SOC and AN to total Nitrogen (TN) were found in the earthworm + Sphingobacterium sp. treatments as well. In non-contaminated soil, Sphingobacterium sp. and earthworms mainly influenced β-glucosidase (BG), urease (URE), N-acetyl-β-d-glucosaminidase (NAG) activities and fluorescein diacetate hydrolysis (FDA) hydrolysis, while in Cd-contaminated soil, they mainly influenced invertase (INV), NAG, URE, and protease (PRO) activities. Principal component analysis indicated that in non-contaminated soil, the earthworm activities dominated the mineralization processes of soil carbon and nitrogen, and Sphingobacterium sp. can intensify this process when it was inoculated in soil along with earthworms. Furthermore, both earthworm species increased C and N levels by elevated INV and PRO activities in combined inoculation. However, in contaminated soil, the impact of earthworm inoculation on soil C stabilization showed a species dependent pattern. E. fetida reduced C mineralization by decreasing URE activities, while A. gracilis enhanced C stabilization by increasing INV activities and decreasing PRO activities. In conclusion, earthworms played a key role in enhancing C and N mineralization in non-contaminated soil and promoting C stabilization in contaminated soil. Both earthworm species followed similar strategies in the former process but adopted different strategies in the latter. When introduced individually, Sphingobacterium sp. was able to promote mineralization in both soils, primarily assisting earthworms in improving carbon and nitrogen mineralization in non-contaminated soil but hindering these processes in Cd-contaminated soil. These findings provide insights into the combined effects of earthworms and microorganisms on carbon and nitrogen cycling.

Multivariate analysis of physical–chemical and biological parameters along wheat growth (Triticum aestivum L.) and the effects of a phosphorus‐solubilizing bioinoculant

AbstractTwo plots (10 ha each) of Triticum aestivum L. wheat crop were analysed, one with a phosphorus‐solubilizing bioinoculant (bioinput) and another without the bioinput (control). Traditional physical–chemical variables and four enzymes were analysed: arylsulfatase (AS), β‐glucosidase (β‐G), acid phosphatase (AP), and N‐acetyl‐β‐d‐glucosaminidase (NAG). These variables were considered by Hierarchical Cluster Analysis (HCA) and partial least squares‐discriminant analysis (PLS‐DA). The HCA separated 100% correctly the control and bioinput samples along the wheat phenological stages (Feekes‐Large scale). The PLS‐DA model was constructed with seven latent variables and obtained 100% accuracy, explaining a variance of 97.05% in calibration and 93.13% in cross‐validation. The control soil had a productivity of 57.8 bags per hectare, while the soil with bioinput had a productivity of 60.8 bags per hectare. Furthermore, soil with the bioinput presented higher concentrations of the enzymes AS, β‐G, and AP in the final phenological stages.

Nephroprotective effects of diminazene on doxorubicin-induced acute kidney injury in rats

This study aimed to investigate the potential protective effects of diminazene, an activator of angiotensin II converting enzyme (ACE2), on kidney function and structure in rats with acute kidney injury (AKI) induced by the anticancer drug doxorubicin (DOX). The impact of diminazene was compared to that of two other drugs: the ACE inhibitor lisinopril and the angiotensin II type 1 (AT1) receptor blocker valsartan. Rats were subjected to a single intraperitoneal injection of DOX (13.5 mg/kg) on the 5th day, either alone or in combination with diminazene (15 mg/kg/day), lisinopril (10 mg/kg/day), or valsartan (30 mg/kg/day) for 8 consecutive days. Various markers related to kidney function, oxidative stress, and inflammation were measured in plasma and urine. Additionally, kidney tissues were assessed histopathologically. DOX-induced nephrotoxicity was confirmed by elevated levels of plasma urea, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL). DOX also led to increased urinary N-acetyl-β-D-glucosaminidase (NAG) activity and decreased creatinine clearance, albumin levels, and osmolality. Moreover, DOX caused a reduction in renal oxidative stress markers, including superoxide dismutase (SOD), glutathione reductase (GR), and catalase activities, while increasing malondialdehyde (MDA) levels. It also raised plasma inflammatory markers, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β). Concurrently administering diminazene significantly mitigated these DOX-induced changes, including histopathological alterations like renal tubule necrosis, tubular casts, shrunken glomeruli, and increased renal fibrosis. Similar protective effects were observed with lisinopril and valsartan. These protective effects, at least in part, appear to result from the anti-inflammatory and antioxidant properties of these drugs. In summary, this study suggests that the administration of diminazene, lisinopril, or valsartan had comparable effects in ameliorating the biochemical and histopathological aspects of DOX-induced acute kidney injury in rats.

Effects of Cecropia pachystachya on inflammatory angiogenesis induced by synthetic implants in mice

This study aimed to evaluate the potential of the hydroethanolic extract of C. pachystachya (HE) in influencing inflammatory angiogenesis and various stages of the inflammatory process. The results demonstrated that HE 5% exhibited a gradual development of angiogenic fibrovascular tissue, as evidenced by increased blood flow and hemoglobin content. Laser Doppler perfusion imaging (LDPI) revealed enhanced blood flow in both HE 2% and 5% groups. Myeloperoxidase (MPO) activity was comparable between HE 2% (0.599 + 0.056 OD/mg wet weight), HE 5% (0.527 + 0.031 OD/mg wet weight), and control groups (0.614 + 0.036 OD/mg wet weight). Conversely, N-acetyl-β-d-glucosaminidase (NAG) activity was significantly increased in the HE 5% group (0.974 + 0.040 OD/mg wet weight). In comparison, HE 2% (0.737 + 0.008 OD/mg wet weight) and control (0.735 + 0.045 OD/mg wet weight) groups exhibited decreased activity with no statistical difference. Furthermore, HE 5% displayed a notable increase of approximately 30% in collagen deposition. The chromatographic analysis identified the extract's chlorogenic acid and the flavonoids orientin and iso-orientin. In conclusion, HE exhibited promising results in promoting inflammatory angiogenesis, particularly at a concentration of 5%, indicating a pro-angiogenic stimulus. The extract also significantly increased macrophage infiltration and collagen production, suggesting its potential as an adjuvant for wound healing or conditions requiring augmented collagen synthesis.

Short-term perennial peanut integration into bahiagrass system influence on soil microbial-mediated nitrogen cycling activities and microbial co-occurrence networks

Integration of perennial peanuts into warm-season grasslands offers a potential solution to reduce nitrogen (N) fertilizer input and enhance N cycling through soil microbial activities. There is limited information on the changes in soil microbial diversity and communities following the short-term integration of rhizoma perennial peanut (RPP; Arachis glabrata Benth.) into warm-season perennial bahiagrass (Paspalum notatum Flüggé) as well as its impact on N cycling processes. This study investigated changes in N cycling populations and soil microbial communities in bahiagrass-RPP mixtures compared to their monocultures at <2 years after RPP establishment in Spring (March) and Fall (October) seasons. Real-time qPCR was used to quantity N functional groups in the soil involved in nitrification, denitrification, and N2 fixation. DNA amplicon sequencing was employed to examine co-occurrence networks of soil microbes, while activities of soil enzymes [N-Acetyl-β-d-glucosaminidase (NAG) and leucine aminopeptidase (LAP)] involved in N mineralization were also measured. Bahiagrass-RPP mixtures had no effect on N cycling genes. Ammonia oxidizing archaea were the major ammonia oxidizing prokaryotes compared to ammonia oxidizing bacteria in bahiagrass-RPP systems. We found that bahiagrass-RPP mixtures exhibited greater prokaryotic alpha diversity and NAG activities than RPP monoculture. Meanwhile, RPP influenced soil fungal community composition (beta diversity) and enhanced the relative abundance of dominant soil fungal genera (Fusarium, Gibberella, and Humicola). The presence of RPP in bahiagrass systems led to increased negative microbial interactions in microbial occurrence networks. Greater complexities in microbial networks were linked to forage growth season, which was related to enrichment of the relative abundance of Basidiomycota. Our findings showed that RPP has the potential to influence N cycling process in bahiagrass system by altering the abundance of certain N cycling microbes, especially fungal taxa, within 2 years of RPP establishment.

Impact of multi-heavy metal exposure on renal damage indicators in Korea: An analysis using Bayesian Kernel Machine Regression.

Exposure to cadmium (Cd), arsenic (As), and mercury (Hg) is associated with renal tubular damage. People living near refineries are often exposed to multiple heavy metals at high concentrations. This cross-sectional study investigated the association between combined urinary Cd, As, and Hg levels and renal damage markers in 871 residents living near the Janghang refinery plant and in a control area. Urinary Cd, As, Hg, N-acetyl-β-D-glucosaminidase (NAG), and β2-microglobulin (β2-MG) levels were measured. The combined effects of Cd, As, and Hg on renal tubular damage markers were assessed using linear regression and a Bayesian Kernel Machine Regression (BKMR) model. The results of the BKMR model were compared using a stratified analysis of the exposure and control groups. While the linear regression showed that only Cd concentration was significantly associated with urinary NAG levels (β = 0.447, P value < .05), the BKMR model showed that Cd and Hg levels were also significantly associated with urinary NAG levels. The combined effect of the 3 heavy metals on urinary NAG levels was significant and stronger in the exposure group than in the control group. However, no relationship was observed between the exposure concentrations of the 3 heavy metals and urinary β2-MG levels. The results suggest that the BKMR model can be used to assess the health effects of heavy-metal exposure on vulnerable residents.

Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity.

Recent studies suggest that the association of antigens in microparticles increases the anti-Leishmania vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly(D,L-lactic) acid submicrometric particles (SMP) and analyze the inflammatory profile and toxicity. Two formulations were selected, SMP1, containing poly(D,L-lactide) (PLA) 1% wt/v and chitosan 1% wt/v; and SMP2, containing PLA 5% wt/v and chitosan 5% wt/v. After a single dose of the unloaded SMP1 or SMP2 in mice, the SMPs promoted cell recruitment without tissue damage. In addition, besides the myeloperoxidase (MPO) activity having demonstrated similar results among the analyzed groups, a progressive reduction in the levels of N-acetyl-β-D-glucosaminidase (NAG) until 72 h was observed for SMPs. While IL-6 levels were similar among all the analyzed groups along the kinetics, only the SMPs groups had detectable levels of TNF-α. Additionally, the Leishmania braziliensis antigen was encapsulated in SMPs (SMP1Ag and SMP2Ag), and mice were vaccinated with three doses. The immunogenicity analysis by flow cytometry demonstrated a reduction in NK (CD3-CD49+) cells in all the SMPs groups, in addition to impairment in the T cells subsets (CD3+CD4+) and CD3+CD8+) and B cells (CD19+) of the SMP2 group. The resulting data demonstrate that the chitosan-coated SMP formulations stimulate the early events of an innate immune response, suggesting their ability to increase the immunogenicity of co-administered Leishmania antigens.

The Protective Potential of Aronia melanocarpa L. Berry Extract against Cadmium-Induced Kidney Damage: A Study in an Animal Model of Human Environmental Exposure to This Toxic Element.

The impact of cadmium (Cd) on the function and structure of the kidney and the potential protective effect of an extract from Aronia melanocarpa L. berries were investigated in a rat model of low- and moderate-level environmental exposure to this heavy metal (1 and 5 mg Cd/kg feed for up to 24 months). The sensitive biomarkers of Cd-induced damage to the kidney tubules (N-acetyl-β-D-glucosaminidase (NAG), alkaline phosphatase (ALP), β2-microglobulin (β2-MG), and kidney injury molecule-1 (KIM-1) in the urine), clinically relevant early markers of glomerular damage (albumin in the urine and creatinine clearance), and other markers of the general functional status of this organ (urea, uric acid, and total protein in the serum and/or urine) and Cd concentration in the urine, were evaluated. The morphological structure of the kidney and inflammatory markers (chemerin, macrophage inflammatory protein 1 alpha (MIP1a), and Bcl2-associated X protein (Bax)) were also estimated. Low-level and moderate exposure to Cd led to damage to the function and structure of the kidney tubules and glomeruli. The co-administration of A. melanocarpa berry extract significantly protected against the injurious impact of this toxic element. In conclusion, even low-level, long-term exposure to Cd poses a risk of kidney damage, whereas an intake of Aronia berry products may effectively protect from this outcome.

Cytokine Profile and Enzymes of Tubular Nephrothelium in the Urine of Children with Congenital Megaureter

The objective: to determine the concentration of transforming growth factor β1 (TGF-β1), interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α), activity levels of tubular nephrothelium enzymes total N-acetyl-β-D-glucosaminidase (NAG), its thermostable NAG isoenzyme B (NAG-B), β-galactosidase (β-Gal), γ-glutamyl transpeptidase (GGT) and neutral α-glucosidase (Nα-Gl) as cytokine-enzymological risk criteria for the development of nephrofibrosis in the urine of children with congenital nonrefluxing megaureter (NRMU) and refluxing megaureter (RMU) with unilateral and bilateral localization of the pathological process. Materials and methods. 174 patients with congenital MU were examined, who were divided into two groups. Group 1 included 131 children with NRMU, group 2 – 43 children with RMU aged from 6 months to 15 years. The control group included 25 practically healthy children. There were 97 patients with unilateral NRMU (group 1a), with bilateral – 34 persons (group 1b); there were 16 patients with unilateral RMU (group 2a), with bilateral – 27 (group 2b). Cytokine and enzyme indicators were studied in the morning portion of urine before reconstructive treatment. The levels of cytokines were determined by the ELISA method. Enzyme activity of urine was determined by the colorimetric method. Statistical processing of data was performed after analyzing the conformity of their distribution to the norm parameters. Results. It was found that the levels of TGF-β1, IL-1β and TNF-α, as well as the activity levels of NAG, NAG-B, β-Gal, GGT and Nα-Gl in the urine of patients with both congenital NRMU and congenital RMU are significantly increased compared to similar indicators in the control group (p&lt;0.001). In patients with congenital RMU, compared to similar average indicators of patients with congenital NRMU, there is a significant increase of all cytokine and enzyme parameters (р&lt;0.05–0.001), which indicates the probability of ischemic-hypoxic, as well as fibrotic damages in the kidney parenchyma in children with MU, especially in patients with RMU. A significant increase in the cytokine levels and enzyme activity levels were established in patients with NRMU and RMU with a unilateral process compared to similar control data (p&lt;0.001. A statistically significant increase of TNF-α, the activity of NAG-B and β-Gal in patients with bilateral NRMU, the concentration of IL-1β, TNF-α and activity levels of NAG, NAG-B, β-Gal, GGT and Nα-Gl in patients with bilateral RMU compared with similar data in groups of patients with unilateral process was found (p&lt;0.05–0.001). Conclusions. Congenital MU (NRMU, RMU) negatively affects the function of the tubular nephrothelium, which is manifested by an increased level of profibrogenic cytokine TGF-β1 and pro-inflammatory cytokines IL-1β and TNF-α in the urine of children, as well as the activity levels of lysosomal enzymes NAG, NAG-B, β-Gal and brush border enzymes GGT and Nα-Gl, which have renal specific properties. This indicates a high probability of ischemic processes in the kidney parenchyma and the risk of nephrofibrosis development in these patients, especially in patients with RMU with bilateral localization of the pathological process.

Peculiarities of Changes in the Activity Levels of Renospecific Enzymes in the Urine of Patients with Ureterolithiasis

The objective: to study the peculiarities of changes in the activity levels of the renal specific enzymes N-acetyl-β-D-glucosaminidase (NAG) and β-galactosidase (β-Gal) as indicators of the functional state of the kidney parenchyma in the urine of patients with ureterolithiasis, depending on the mineral composition of the calculi and their localization in the ureter Materials and methods. 81 patients were examined for unilateral ureterolithiasis (45 men, 36 women), the average age of the patients was 43.2±9.7 years. In the studied patients, the stone sizes were on average 1.1±0.38 cm. The activity of NAG and β-Gal was determined in the urine before the stone was removed. All patients were divided into groups: 1st group – 33 patients with calcium oxalate stones, 2nd group – 18 persons with uric acid stones, 4th group – 12 patients with phosphate stones. The control group included 28 practically healthy people. Depending on the location of the calculus, the patients were divided into subgroups: localization of stones in the upper third of the ureter – subgroup 1a (n=17), in the middle third – subgroup 2a (n=23), in the lower third of the ureter – subgroup 3a (n=41). Urine for analysis was obtained during catheterization of the ureter from the side affected by the stone, before the use of medical agents and after physiological urination. Results. The activity levels of NAG and β-Gal in the urine from the side affected by the calculus (renal pеlvis) in 81 patients were statistically significantly different from similar indicators in the urine from the bladder after physiological urination in the same patients (р&lt;0.001–0.02). In the urine of patients with unilateral ureterolithiasis, there were no significant changes in the activity levels of NAG and β-Gal depending on the mineral composition of the calculi, with the exception of patients with phosphate urolithiasis. The intensity of activity levels (both NAG and β-Gal) in the urine of these patients was most high in the upper third of the ureter (group 1a), the less high – in the lower third of the ureter (group 3a), the difference was statistically significant (р&lt;0.001–0.02). Conclusions. The analysis of changes in the levels of urinary activity of NAG and β-Gal allows to objectively assess the functional state of the tubular nephrothelium in patients with ureterolithiasis before surgical intervention, and in the post-treatment period will help to monitor the effectiveness of treatment.