Search Results (72)

Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-β-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms. Full article

This study investigates the effects of different land-use types (forest, arable land, and wetland) on key soil properties, microbial communities, and nitrogen cycling in the Lesser Khingan Mountains. The results revealed that forest (FL) and wetland (WL) soils had significantly higher soil organic matter (SOM) content compared with arable land (AL), with total phosphorus (TP) being highest in FL and available nitrogen (AN) significantly higher in WL. In terms of enzyme activity, AL and WL showed reduced activities of ammonia monooxygenase (AMO), β-D-glucosidase (β-G), and β-cellobiosidase (CBH), while exhibiting increased N-acetyl-β-D-glucosaminidase (NAG) activity, highlighting the impact of land use on nitrogen dynamics. WL also exhibited significantly higher microbial diversity and evenness compared with FL and AL. The dominant bacterial phyla included Actinobacteriota, Proteobacteria, and Acidobacteriota, with Acidobacteriota being most abundant in FL and Proteobacteria most abundant in WL. Network analysis showed that AL had the most complex and connected microbial network, while FL and WL had simpler but more stable networks, suggesting the influence of land use on microbial community interactions. Regarding nitrogen cycling genes, AOA-amoA was most abundant in AL, while AOB-amoA was significantly enriched in FL, reflecting the influence of land use on ammonia oxidation. These findings highlight how land-use types significantly affect soil properties, microbial community structures, and nitrogen cycling, offering valuable insights for sustainable land management. Full article

Riociguat is a soluble guanylate cyclase (sGC) activator that increases the levels of cyclic guanosine monophosphate (cGMP). cGMP is known to play a key role in regulating kidney function. This research sought to investigate the possible protective effects of riociguat on the kidneys in the context of chronic kidney disease (CKD). CKD was induced in male Wistar rats through adenine administration. A total of 24 rats were allocated into four groups and administered treatments over a period of 35 days. Group 1 received a normal diet and a vehicle (carboxymethylcellulose (0.5%)), serving as the control. Group 2 received adenine (0.25% w/w) in the feed and a vehicle. Groups 3 and 4 received adenine in the feed (0.25% w/w) plus riociguat (3 mg/kg/day) and riociguat (10 mg/kg/day), respectively. Adenine administration significantly elevated systolic blood pressure, plasma creatinine, urea, and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, adenine reduced creatinine clearance and increased the urinary albumin-to-creatinine ratio and urinary N-Acetyl-β-D-Glucosaminidase (NAG). Histopathologically, adenine caused renal tubular necrosis and fibrosis. Furthermore, adenine elevated the plasma concentration of interleukins (IL-1β and IL-6) and tumor necrosis factor-alpha (TNF-α). Adenine significantly increased renal malondialdehyde (MDA) and reduced glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC). Treatment with riociguat attenuated adenine-induced hypertension, improved kidney function, and ameliorated histopathological changes. Riociguat also reduced kidney injury markers, inflammation, and renal oxidative stress. The renoprotective effect of riociguat is probably due to anti-inflammatory and antioxidant actions. This indicates that riociguat may have the potential to slow the progression of kidney damage in chronic kidney disease (CKD). Full article

The aim of this study was to analyse the effect of intramammary infection (IMI) on N-acetyl-β-D-glucosaminidase (NAGase) enzyme values and to study its predictive capacity using different algorithms. To do this, 26 sheep free of intramammary infection were selected, and their somatic cell count (SCC), NAGase and bacteriological culture were monitored for 2 weeks. They were then subjected to a series of unhealthy situations (UHS) for the mammary gland, and these variables were monitored for a further 4 weeks. IMI was established in 12 of the 26 sheep. In the 4 days following infection, a very marked increase in enzyme values was observed in the infected glands. The algorithm that obtained the best result was the one that detected, in at least two of the first four days after infection, an increase in NAGase values greater than 30% compared to the average of the 3 days prior to infection, obtaining an area under the curve (AUC) of 0.90, an accuracy of 89.8%, a sensitivity of 95.2% and a specificity of 85.7%. Full article

Efficient nitrogen management is crucial for improving corn productivity while minimizing environmental impacts. This study evaluates the response of corn to nitrogen fertilization using three key metrics: yield; nitrogen harvest index (NHI); and agronomic nitrogen use efficiency (ANUE). This experiment was conducted over three years (2021–2023) across 84 sites in Quebec, Canada, with five nitrogen treatments applied post-emergence (0, 50, 100, 150, 200 kg N/ha) and initial nitrogen applied at seeding (30 to 60 kg/ha). In addition, various soil health indicators, including physical, chemical, and biochemical properties, were monitored to understand their interaction with nitrogen use efficiency. Machine learning techniques, such as augmented extreme learning machine (AELM) and particle swarm optimization (PSO), were employed to optimize nitrogen recommendations by identifying the most relevant features for predicting yield and nitrogen use efficiency (NUE). The results highlight that integrating soil health indicators such as enzyme activities (β-glucosidase [BG] and N-acetyl-β-D-glucosaminidase [NAG]) and soil proteins into nitrogen management models improves prediction accuracy, leading to enhanced productivity and environmental sustainability. These findings suggest that advanced data-driven approaches can significantly contribute to more precise and sustainable nitrogen fertilization strategies. Full article

Pogostemon cablin (Patchouli), an essential medicinal plant in the Lamiaceae family, faces significant challenges under continuous cropping (CC) obstacles. This study examined the rhizospheric soil bacterial communities of patchouli under four different CC years, zero (CK), one (T1), two (T2), and three (T3) years through high-throughput 16S rRNA gene amplicon sequencing. Results showed long-term CC led to significant soil properties and enzyme activity shifts. Key parameters such as soil pH and total potassium (TK) decreased, while ammonium nitrogen (NH₄⁺–N), soil organic carbon (SOC), nitrate nitrogen (NO₃⁻–N), available potassium (AK), available phosphorus (AP), total nitrogen (TN), and total phosphorus (TP) increased over the cropping years. Enzyme activities, including ß-glucosidase (ß-GC), polyphenol oxidase (PPO), catalase (CAT), N-acetyl-β-D-glucosaminidase (NAG), and leucine aminopeptidase (LAP), were notably affected. The CC altered the bacterial community structure and composition, reducing the relative abundance of Proteobacteria, Firmicutes, Actinobacteria, and Planctomycetota over time. These findings highlight the impact of CC on patchouli rhizosphere bacteria, providing insights for improved soil management and fertilization strategies in CC systems. Full article

Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction. The body burden of Cd at which these outcomes occur is not, however, reliably defined. Here, multiple-regression and mediation analyses were applied to data from 737 non-diabetic Thai nationals, of which 9.1% had an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m² (a low eGFR). The excretion of Cd (E_Cd), and renal-effect biomarkers, namely β₂-microglobulin (E_β2M), albumin (E_alb), and N-acetylglucosaminidase (E_NAG), were normalized to creatinine clearance (C_cr) as E_Cd/C_cr E_β2M/C_cr, E_alb/C_cr, and E_NAG/C_cr. After adjustment for potential confounders, the risks of having a low eGFR and albuminuria rose twofold per doubling E_Cd/C_cr rates and they both varied directly with the severity of β₂-microglobulinuria. Doubling E_Cd/C_cr rates also increased the risk of having a severe tubular injury, evident from E_NAG/C_cr increments [POR = 4.80, p = 0.015]. E_NAG/C_cr was strongly associated with E_Cd/C_cr in both men (β = 0.447) and women (β = 0.394), while showing a moderate inverse association with eGFR only in women (β = −0.178). A moderate association of E_NAG/C_cr and E_Cd/C_cr was found in the low- (β = 0.287), and the high-Cd body burden groups (β = 0.145), but E_NAG/C_cr was inversely associated with eGFR only in the high-Cd body burden group (β = −0.223). These discrepancies together with mediation analysis suggest that Cd-induced nephron destruction, which reduces GFR and the tubular release of NAG by Cd, involves different mechanisms and kinetics. Full article

The long-term excessive use of chemical fertilizers may result in soil degradation, but manure and straw application is considered to be an effective approach for alleviating this problem. The aim of this study is to examine the long-term impacts of different fertilization patterns on soil quality variables in a wheat–sweet potato rotation system. Four treatments were conducted in a field trial for a duration of twelve years, including (1) no fertilizer (control, CK); (2) application of mineral fertilizers (NPK) alone; (3) NPK with crop straw return (NPKs); (4) combined use of NPK and farmyard manure (NPKm). Thirteen physical, chemical, and biological soil parameters were measured. The results showed that the NPKm and NPKs significantly improved the proportion of macroaggregates (>0.25 mm) by 24.7% and 21.9% compared to the NPK alone, respectively. The proportion of microaggregates (0.053–0.25 mm) under the NPKm was 47.4% significantly higher than the NPKs. Additionally, the NPKm resulted in a 22.2% and 19.6% increase in the SOC content than the NPK and NPKs, respectively. In terms of soil-available K, the NPKs resulted in levels that were 42.1% and 49.6% higher than the NPKm and NPK alone, respectively. Long-term fertilization significantly decreased soil pH by 0.95–1.85 units compared to the control, whereas manure application could alleviate soil acidification, as shown when the pH increased by 10.6–18.7%. The NPKm and NPKs resulted in significantly increased soil pHs by 10.6% and 18.7% compared to the NPK alone, respectively. In addition, the NPKm and NPKs increased N-acetyl-β-D-glucosaminidase activity by 52.6% and 60.3% compared to the NPK alone. Determined by the minimum data set method, the NPKm treatment exhibited the highest soil quality index, followed by the NPKs and NPK. Our findings suggested that the combined use of chemical fertilizers with organic amendments proved beneficial for enhancing soil quality. Full article

Trichoderma is a soil-dwelling microorganism that has many benefits for plants and is therefore widely used in agriculture. Among the secondary metabolites produced by Trichoderma, gliotoxin (GT) is one of the most studied. The antagonistic effect of GT on other fungi was first discovered by R. Weindling in 1934. He referred to it as the “lethal principle” of Trichoderma. Despite the long history of studying GT, its impact on the soil microbial community has remained largely unexplored. In our work, we investigated the response of the soil microbial community to different doses of GT (10–500 µM per kg) and different durations (7–56 days) of exposure. We measured microbiological parameters (CO₂ emission, microbial biomass (MB)), calculated the eco-physiological indices and determined the activity of soil enzymes involved in the C, N, P and S cycles. We identified three types of microbial responses to GT: inhibition, stress and stimulation. The inhibitory effect developed only by day 56 and in the samples treated with 500 μM GT. The stress effect (increased CO₂ emission and decreased MB) of GT on microbial communities was predominant. Soil extracellular enzymes also responded to GT to varying degrees. A stimulating effect of GT on enzyme activity was noted for β-D-1,4-cellobiosidase and β-1,4-glucosidase. The activity of arylsulfatase and leucine aminopeptidase decreased under the influence of GT up to day 28, but by the end of the experiment, there was a restoration of activity. We did not observe any significant changes in the activity of β-1,4-xylosidase, β-1,4-N-acetyl-glucosaminidase or acid phosphatase. The results obtained showed that GT at high, “man-made” doses can inhibit the microbiological activity of soil, but at naturally occurring concentrations, it can have a stimulating effect on soil microbiome functionality. Full article

Soils are the largest reservoir of microplastics (MPs) on earth. Since MPs can remain in soils for a very long time, their effects are magnified. In this study, different concentrations of polyethylene (PE) MPs derived from commercial resins (0%, 1%, 7%, and 14%, represented as MP_0, MP_1, MP_7, and MP_14) were added to soils to assess the changes in the soils’ chemical properties, enzyme activities, and bacterial communities during a 70-day incubation period. The results show that PE MP treatments with low concentrations differed from other treatments in terms of exchangeable Ca and Mg, whereas at high concentrations, the pH and availability of phosphate ions differed. Fluorescein diacetate (FDA), acid phosphatase (ACP), and N-acetyl-β-d-glucosaminidase (NAG) enzyme activities exhibited a dose-related trend with the addition of the PE MPs; however, the average FDA and ACP activities were significantly affected only by MP_14. Changes in the microbial communities were observed at both the phylum and family levels with all PE MP treatments. It was revealed that even a low dosage of PE MPs in soils can affect the functional microbes, and a greater impact is observed on those that can survive in polluted environments with limited resources. Full article

Background: Diagnosis of acute kidney injury (AKI) relies on serum creatinine (SCr) changes. This study investigated if urinary aminopeptidases are early and predictive biomarkers of cardiac surgery-associated AKI (CSA-AKI). Methods: Glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), proteinuria, albuminuria, N-acetyl-β-D-glucosaminidase (NAG), and neutrophile gelatinase-associated lipocalin (NGAL) were measured in urine samples from 44 patients at arrival in the intensive care unit (ICU) after cardiac surgery. Sensitivity, specificity, and positive and negative predictive value for diagnosis of stages 1, 2, and 3 of AKI were analyzed for the highest quartile of each marker. We also studied the relationship with SCr after surgery, 6- and 12-month glomerular filtration rates (GFRs), and other long-term events over the next 5 years. Results: GluAp diagnosed the maximal number of patients that developed stage 2 or 3 of AKI, increasing diagnostic sensitivity from 0% to 75%. In addition, GluAp and DPP4 were related to the decrease in GFR at 6 or 12 months after surgery. Conclusions: Urinary aminopeptidases are a potential tool for the early diagnosis of CSA-AKI, with GluAp being the most effective marker for diagnosing stage 2 or 3 of AKI at ICU admission. GluAp and DPP4 serve as predictive biomarkers for a decrease in GFR. Full article

Establishing a safe exposure level from epidemiological studies while providing direct hazard characterization in humans often faces uncertainty in causality, especially cross-sectional data. With advances in molecular epidemiology, it is reasonable to integrate identified intermediate biomarkers into health risk assessment. In this study, by considering the mediation of the oxidative stress marker malondialdehyde (MDA), we explored the exposure threshold of melamine on the early renal injury marker N-acetyl-β-D glucosaminidase (NAG). The benchmark dose (BMD) was derived from model averaging of the composite direct effect of melamine exposure and the indirect effect through the mediation of MDA on NAG levels. As illustrative examples, we analyzed 309 adult patients with calcium urolithiasis and 80 occupational workers for the corresponding exposure thresholds. The derived threshold was subpopulation-dependent, with the one-sided lower bound BMDL₁₀ for the patients with urolithiasis with (without) the mediator MDA for the patients with kidney stones and the occupational workers being 0.88 (0.96) $\mathsf{\mu }\mathrm{g}/\mathrm{k}\mathrm{g\_b}\mathrm{w}/\mathrm{d}\mathrm{a}\mathrm{y}$ and 22.82 (18.09) $\mathsf{\mu }\mathrm{g}/\mathrm{k}\mathrm{g\_b}\mathrm{w}/\mathrm{d}\mathrm{a}\mathrm{y}$, respectively. The derived threshold levels, considering the oxidative stress marker MDA, were consistent with those without adjusting for the mediation effect. However, the study outcomes were further supported by the suggested mechanism pathway. The threshold for the patients with urolithiasis was up to two orders lower than the current tolerable daily intake level of 200 $\mathsf{\mu }\mathrm{g}/\mathrm{k}\mathrm{g\_b}\mathrm{w}/\mathrm{d}\mathrm{a}\mathrm{y}$ recommended by the WHO (EFSA). Full article

One of the most serious diseases affecting dairy cattle, causing significant losses both in breeding and economy, is mastitis, an inflammation of the mammary gland. Due to the economic importance of this issue, many research teams are striving to develop an easy-to-apply and, most importantly, effective method to prevent mastitis. The use of traditional methods for mastitis detecting and treating, as well as improvement in hygienic conditions, have not yielded the expected results in combating this disease combating. Currently, the main task is to find the tools that would allow for the rapid detection of mastitis and the improvement of udder health in cows while maintaining high milk production, which is essential for the profitability of dairy cattle farming. Accurate and rapid diagnostic tools, with the simultaneous capability of identifying pathogens, may help to reduce losses. Sufficient sensitivity and specificity for tests are required to minimize the number of false-positive and false-negative cases. Efforts are also being made to determine the optimal threshold value for detecting the disease at its earliest possible stage. The estimation of somatic cell count (SCC) as a phenotypic indicator of mastitis is widely used. A more precise parameter for accurately describing udder health is the differential somatic cell count (DSCC). The well-known California Mastitis Test (CMT) is an inexpensive, easy, and rapid method for mastitis detection useful on farms. The latest diagnostic methods for mastitis utilize tests based on the activity of N-acetyl-β-d-glucosaminidase (NAGase) or lactate dehydrogenase (LDH) as well as the determination of acute phase proteins (APPs) in blood serum and milk (such as haptoglobin, serum amyloid A, fibrinogen, and ceruloplasmin). Research also focuses on the genomic improvement of mastitis resistance in successive generations, and for this purpose, many quantitative trait loci (QTLs) and single nucleotide polymorphisms (SNPs) have been identified. In recent years, immunotherapy has become an increasingly common area of research, including vaccinations, T/B cell immunotherapy, RNA immunotherapy, epigenetic immunotherapy, stem cell therapy, and native secretory factors. An important aspect of the control of mastitis is the implementation of strategies that focus primarily on preventing the disease through appropriate breeding and farm management practices. In the forthcoming years, a significant challenge will be the development of universal diagnostic and therapeutic strategies that can be effectively implemented as alternatives to antibiotic therapy. Future research should prioritize the advancement of preventive and therapeutic techniques, such as immunotherapies, bacteriocins, herbal therapy, and nanoparticle technology. Full article

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-β-(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. Full article

In the dairy industry, bovine mastitis represents a major concern due to substantial production losses and costs related to therapies and early culling. The mechanisms of susceptibility and effective response to intra-mammary infections are still poorly understood. Therefore, we investigated innate immunity in acellular bovine skim milk through cytofluorimetric analyses of bacterial killing activity against both Gram-positive and Gram-negative pathogens. Freshly cultured E. coli and S. aureus strains were incubated with colostrum and milk samples at different lactation time points from two groups of cows, purportedly representing mastitis-resistant and mastitis-susceptible breeds; bacterial cells were analyzed for vitality by flow cytometry following incorporation of vital dyes. N-acetyl-β-D-glucosaminidase (NAGase) activity was also investigated in milk and colostrum samples. Our findings revealed that colostrum and milk bacterial killing activity was greater against S. aureus compared to E. coli., with this activity correlated with milk NAGase levels. Furthermore, both killing of S. aureus and NAGase activity were negatively correlated to the elapsed time of lactation. Interestingly, samples from the allegedly mastitis-resistant breed displayed higher bacterial killing and NAGase activities. Our study suggests that diverse control mechanisms are exerted against Gram-positive and Gram-negative pathogens in the mammary glands of cows, probably beyond those already described in the literature. Full article