Stress Biomarkers Research Articles

Repeated intravesical injections of platelet-rich plasma are safe and effective in the treatment of interstitial cystitis/bladder pain syndrome

ABSTRACT Objectives: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a challenging chronic inflammatory condition affecting the urinary bladder, with limited treatment options. This study aims to assess the clinical efficacy of repeated intravesical platelet-rich plasma (PRP) injections for promoting urothelial regeneration and reducing inflammation in patients with IC/BPS and investigate its correlation with subjective and objective treatment-related outcomes. Materials and Methods: Four monthly intravesical PRP injections were given to 98 patients with non-Hunner-type IC/BPS. Treatment outcomes were assessed using a global response assessment (GRA) score 3 months posttreatment. In addition, clinical symptom scores, pain severity, voiding diary data, uroflowmetry parameters, and GRA scores were compared before and after treatment and between different treatment outcome groups (satisfactory: GRA≥2 unsatisfactory: GRA<2). Baseline urine biomarkers were analyzed to identify potential treatment outcome predictors. Results: After four PRP injections, 54 (55.1%) patients reported satisfactory outcomes. Lower urinary tract symptoms, bladder pain, urinary frequency, anxiety, and flow rate significantly improved from baseline (P < 0.05) in all patients, regardless of the treatment outcome. All patients experienced improved treatment outcomes and increased maximum bladder capacity with successive PRP treatments, and no major complications were reported. Urine biomarkers indicated elevated inflammation and oxidative stress biomarkers in patients with IC/BPS compared to controls. Conclusion: Repeated PRP injections are safe and effective for reducing symptoms and bladder pain and improving bladder capacity in a majority of IC/BPS patients, with better outcomes observed in patients with a mild form of bladder inflammation. These results support PRP as a promising novel bladder therapy for IC/BPS.

Genotype-Dependent Variations in Oxidative Stress Markers and Bioactive Proteins in Hereford Bulls: Associations with DGAT1, LEP, and SCD1 Genes.

The objective of this study is to assess the influence of genetic polymorphisms in DGAT1, LEP, and SCD1 on the oxidative stress biomarkers and bioactive protein levels in Hereford bulls. A total of sixty-eight bulls were analyzed at 22 months of age to assess growth metrics and carcass quality, with a focus on polymorphisms in these genes. The key markers of oxidative stress, including malondialdehyde (MDA), and the activities of antioxidant enzymes such as glutathione reductase (GluRed), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were measured, alongside bioactive compounds like taurine, carnosine, and anserine. The results show that the TT genotype of DGAT1 is linked to significantly higher MDA levels, reflecting increased lipid peroxidation, but is also associated with higher GluRed and GPx activities and elevated levels of taurine, carnosine, and anserine, suggesting an adaptive response to oxidative stress. The LEP gene analysis revealed that the CC genotype had the highest MDA levels but also exhibited increased GPx and SOD activities, with the CT genotype showing the highest SOD activity and the TT genotype the highest total antioxidant status (TAS). The SCD1 AA genotype displayed the highest activities of GluRed, GPx, and SOD, indicating a more effective antioxidant defence, while the VA genotype had the highest MDA levels and the VV genotype showed lower MDA levels, suggesting protective effects against oxidative damage. These findings highlight genotype specific variations in the oxidative stress markers and bioactive compound levels, providing insights into the genetic regulation of oxidative stress and antioxidant defences, which could inform breeding strategies for improving oxidative stress resistance in livestock and managing related conditions.

Insights into the Novel Biomarkers Expressed in Diabetic Nephropathy: Potential Clinical Applications.

Diabetic nephropathy (DN) is increasing worldwide in parallel with type 2 diabetes mellitus. Identifying diagnostic biomarkers for DN at an early stage is crucial due to the considerable societal and economic burden associated with diabetes mellitus (DM) and its risk factors. In the past, early indicators of microvascular problems, such as microalbuminuria (MA), have been used to predict the possibility of developing advanced chronic kidney disease (CKD). However, because of the incapacity of MA to appropriately estimate DN, particularly, non-albuminuric DN, additional markers have been suggested for recognizing the early renal abnormalities and structural lesions, even before MA. This study aims to assess the existing and future biomarkers used to diagnose or predict early DN. This review provides comprehensive insight into diagnostic approaches for early detection of CKD, addressing the following areas: (i) markers of glomerular damage, (ii) markers of tubular damage, (iii) oxidative stress biomarkers, (iv) inflammatory biomarkers and (v) futuristic biomarkers such as micro-ribonucleic acids (miRNAs), proteomics, metabolomics and genomics and gut microbiota. Early detection of DN may lead to improvement in clinical management and quality of life, emphasizing the importance of identifying a specific and reliable predictive biomarker. Emerging serum and urinary biomarkers offer promise for early DN diagnosis, potentially reducing prevalence and preventing progression to end-stage renal disease (ESRD). Further advancements in miRNAs, proteomics, metabolomics genomics and gut microbiota offer prospects for even earlier and more precise DN diagnosis.

Protective effect of Tecoma stans (L.) Juss.ex Kunth in CFA-induced arthritic rats

Ethnopharmacological relevanceTecoma stans (L.) Juss.ex Kunth (Bignoniaceae) is mainly found in tropical and subtropical regions of Africa and Asia. The leaves, flowers, roots, and bark are used to treat various aliments includes, skin infections, kidney problems, intestinal disorders, jaundice, toothaches, joint pain and repair cracked bones, antidotes for snake, scorpion, and rat bites. Aim of the studyThe objective of the study is to assess the anti-arthritic properties of T. stans leaf using Complete Freund's adjuvant (CFA)-induced rat. Materials and methodThe ethanol extract of T. stans leaf (ETSL) was subjected toGas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis for the identification of potential bioactive. The anti-arthritic activity was carried out by administering CFA (0.1 ml) into the sub-plantar surface of the right hind paw. The experimental animals were treated with indomethacin (10 mg/kg) and ETSL (250, 500 mg/kg) once a day orally for fourteen days. The arthritic parameters and hematological and biochemical parameters were evaluated using standard kit reagents. The levels of pro-inflammatory cytokines and inflammatory mediators were measured in blood serum. Antioxidant parameters were assessed in homogenized liver and joint tissues. Radiological and histopathological analysis of joint was performed. A computational molecular docking investigation of the phytoconstituents was conducted against COX-2, IL-1β, IL-6, and TNF-α receptors. ResultsThe ETSL at 500 mg/kg demonstrated significant (p < 0.01) restoration of arthritic parameters, hematological and biochemical indices and oxidative stress in CFA-induced rats which was further supported by radiological histological examination. In addition, there was significant (p < 0.05) reduction observed in pro-inflammatory cytokines, inflammatory mediators and up-regulation of anti-inflammatory cytokines in the treated group. Verbascoside was found to exhibit better biding affinities −10.4, −7.4, −7 and −6.2 kcal/mol against COX-2, IL-1β, TNF-α, and IL-6 respectively, confirmed through in silico study. ConclusionsThe observed outcome suggests that ETSL at a dosage of 500 mg/kg demonstrated notable anti-arthritic effects by suppressing pro-inflammatory cytokines and oxidative stress biomarkers. This effect could potentially be attributed to the presence of bioactive verbascoside identified in the LC-MS analysis.

Response of oxidative stress and neurotoxicity biomarkers in rainbow trout (Oncorhynchus mykiss) after exposure to six-metal mixtures

ABSTRACT The activity of liver catalase and brain acetylcholinesterase was assessed in rainbow trout (Oncorhynchus mykiss) after 7- and 14-day exposure to a six-metal mixture at the maximum permissible concentrations accepted for inland waters in the EU (2013/39/EU; 2008/105/EC) (Zn − 0.1, Ni − 0.034, Cu − 0.01, Cr − 0.01, Cd − 0.0015 and Pb − 0.014 mg L−1) and to the same six-metal mixtures with tenfold reduced concentration of Cu and Cr ions. A statistically significant increase of up to 26% of catalase and 52% of acetylcholinesterase activity was observed in rainbow trout after 7 days of exposure to the six-metal mixture at the maximum permissible concentrations in comparison to a control group. After 14-day treatment, neither CAT nor AChE showed significant response to all tested metal mixtures. The six-metal mixture with the tenfold reduced concentration of Cr increased brain AChE activity in O. mykiss after 7 days of exposure (35%). Enhancement of catalase activity caused by the mixture of the six metals at the maximum permissible concentrations and the increased acetylcholinesterase activity in response to the same metal mixture and mixture with tenfold reduced Cr concentration after 7 days of exposure indicates the induction of oxidative stress and disturbance of cholinergic system homeostasis respectively.

The impact of inflammatory and oxidative stress biomarkers on the sympathetic nervous system in severe coronary atherosclerosis.

The present study aimed at evaluating the association between sympathetic nervous system activation (SNS) and the severity of coronary artery disease (CAD). In addition, we tested the hypothesis that inflammation and oxidative stress influence the SNS activation. Adult patients with severe CAD scheduled for coronary artery bypass graft (CABG) surgery were enrolled. SYNTAX I score was calculated based on coronary angiography. Systemic activation of the SNS was estimated through circulating levels of norepinephrine (NE). Plasma levels of pro-inflammatory cytokines (IL 1β, IL 6 and HIF 1α) and oxidative stress molecules (SOD-1 and LOX-1) were obtained prior to surgery. Circulating NE levels were significantly correlated with the severity of CAD, as assessed by the SYNTAX I score (p 0.002; r 0.329). Elevated levels of circulating pro-inflammatory markers were significantly correlated with increased NE concentrations (for IL-1β: p < 0.001, r = 0.49; for IL-6 and NE: p = 0.003, r = 0.32; for HIF-1α and NE: p = 0.049, r = 0.21). Additionally, oxidative stress molecules were associated with circulating NE levels (for SOD-1 and NE: p = 0.016, r = 0.26; for LOX-1 and NE: p = 0.004, r = 0.31). In patients with CAD referred for CABG, SNS activation, indicated by plasma NE levels, was correlated with disease severity as assessed by the SYNTAX I score, as well as with markers of inflammation and oxidative stress. This suggests that inflammation, oxidative stress, and SNS activation form an interconnected network, with each component influencing the others. It might be of interest to develop a scoring system including inflammation and oxidative stress markers to identify patients that require a more aggressive approach to lower inflammation, oxidative stress and modulate the sympathetic nervous system. This could be of use especially in the setting of a scheduled intervention -such as CABG surgery.

SLC30A2-Mediated Zinc Metabolism Modulates Gastric Cancer Progression via the Wnt/β-Catenin Signaling Pathway.

Gastric cancer (GC) is a significant global health burden with limited treatment options. The purpose of this study was to investigate the role of SLC30A2, a zinc transporter, in GC development and its capacity as a target for therapy. A comprehensive analysis of GC datasets (GSE54129 and stomach adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA)) was conducted using bioinformatics tools to examine differential gene expression, focusing on SLC30A2. Functional assays, including Cell counting kit-8 (CCK-8) and transwell assays, were carried out on GC cell lines to determine the impact of SLC30A2 knockdown on cell behavior. Flow cytometry was utilized to quantitatively observe cell apoptosis and cell cycle progression. The impact of zinc sulfate (ZnSO4) on GC cells was evaluated by detecting apoptosis markers, Wnt/β-catenin signaling pathway activity, and oxidative stress biomarkers, focusing on the regulatory effect of SLC30A2 overexpression. Our analysis revealed significant upregulation of SLC30A2 in GC samples compared to normal samples, and high SLC30A2 expression was linked to poor prognosis. SLC30A2 knockdown repressed proliferation, invasion, and migration of GC cells, induced apoptosis, as well as arrested the cell cycle. Additionally, ZnSO4 treatment induced cytotoxicity and oxidative stress in GC cells, while SLC30A2 overexpression rescued ZnSO4-induced, migration, invasion, and proliferation. Moreover, ZnSO4 had been shown to bolster apoptosis and trigger the Wnt/β-catenin signaling pathway, effects which were mitigated by the overexpression of SLC30A2. Our results implied that SLC30A2 was essential for GC progression by modulating zinc homeostasis and cellular processes. Targeting SLC30A2 or zinc signaling may represent a potential therapeutic approach for GC treatment.

A geo-gender-based analysis of human health: The presence of cut flower farms can attenuate pesticide exposure in African communities, with women being the most vulnerable.

The rapid expansion of the cut flower industry in Africa has led to pervasive use and potential exposure of pesticides, raising concerns for local communities. Whether the risks associated with pesticide applications are localised or have broader implications remains unclear. We measured biomarkers of real and perceived pesticide exposure in two Kenyan communities: Naivasha, where the cut flower industry is present, and Mogotio, where the cut flower industry is absent. We measured real exposure by the percentage of acetylcholinesterase (AChE) inhibition and perceived exposure by assessing hair cortisol levels, a biomarker of stress. Additionally, we conducted a demographic survey to evaluate the health and socioeconomic status of participants, as well as their perceptions of pesticide risks associated with the cut flower industry. Perceived pesticide exposure was more common in Naivasha (n = 36, 56%) compared to Mogotio (n = 0, 0%), according to community surveys. However, Mogotio residents had significantly higher mean hair cortisol levels (mean (x̄) = 790 ng/g, standard deviation (SD) = 233) and percentage of AChE inhibition (x̄ = 28.5%, SD = 7.3) compared to Naivasha residents, who had lower mean hair cortisol levels (x̄ = 548 ng/g, SD = 187) and percentage of AChE inhibition (x̄ = 14.5%, SD = 10.1). Location (proximity to cut flower farms) and gender were significant factors influencing pesticide exposure, with individuals living outside the cut flower industrial complexes being at higher risk. Women in both communities were the most vulnerable demographic, showing significantly higher mean hair cortisol levels (x̄ = 646 ng/g, SD = 267.4) and percentage of AChE inhibition (x̄ = 22.5%, SD = 12.4) compared to men hair cortisol levels (x̄ = 558.2 ng/g, SD = 208.2) and percentage of AChE inhibition (x̄ = 10.4%, SD = 13.1). A heightened awareness of the potential risks of pesticide exposure was widespread within cut flower industrial complexes. This may have led to a reduction in exposure of both workers and non-workers living within or close to these complexes. In contrast, communities living outside these complexes showed higher levels of exposure, possibly due to limited chemical awareness and a lack of precautionary measures. Despite this contrast between communities, women remained the most vulnerable members, likely due to their socioeconomic roles in African society. Monitoring women's pesticide exposure is crucial for providing an early warning system for community exposure.

Torsion-Induced Traumatic Optic Neuropathy (TITON): A Physiologically Relevant Animal Model of Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) is a common cause of irreversible blindness following head injury. TON is characterized by axon damage in the optic nerve followed by retinal ganglion cell death in the days and weeks following injury. At present, no therapeutic or surgical approach has been found to offer any benefit beyond observation alone. This is due in part to the lack of translational animal models suitable for understanding mechanisms and evaluating candidate treatments. In this study, we developed a rat model of TON in which the eye is rapidly rotated, inflicting mechanical stress on the optic nerve and leading to significant visual deficits. These functional deficits were thoroughly characterized up to one week after injury using electrophysiology and immunohistochemistry. The photopic negative response (PhNR) of the light adapted full field electroretinogram (LA ffERG) was significantly altered following injury. This correlated with increased biomarkers of retinal stress, axon disruption, and ganglion cell death. Together, this evidence suggests the utility of our model for mimicking clinically relevant TON and that the PhNR may be an early diagnostic for TON. We also found indirect evidence that ketamine, which was used for anesthesia, may ameliorate TON. Future studies will utilize this animal model for evaluation of candidate treatments.

Nucleotide sequence variants, gene expression and serum profile of immune and antioxidant markers associated with bacterial diarrhea susceptibility in Barki lambs

BackgroundDespite the fact that diarrhea is more accurately described as a clinical symptom than a disease. Diarrhea is one of the most important issues in ovine medicine, particularly in lambs, and because of high morbidity and mortality rate, sluggish growth performance, and veterinary costs, it is believed to be a major source of economic loss. Salmonella and enterotoxigenic Escherichia coli are the most common and commercially significant agents responsible for diarrhea.ObjectiveThe objective of this study was to monitor the nucleotide sequence variations, gene expression, serum inflammatory and oxidative stress biomarkers in diarrheic lambs. Another aim was to identify different pathotypes and virulence genes of Salmonella and E. coli causing diarrhea.MethodologyBlood samples were taken from 50 Barki who were diarrheal and 50 who appeared to be healthy, and then divided in 3 portions, with EDTA added to the first part for CBC, DNA and RNA extraction. The second sample received 5000 I.U. of heparin calcium, and a clean plain tube was used for the third component. The second and third sections were centrifuged to extract serum and plasma until the biochemical and immunological analysis was completed. Fecal samples were collected for bacteriological examination, and the bacteria were identified by PCR analysis. PCR-DNA sequencing was conducted for immune (SELL, JAK2, SLC11A1, IL10, FEZF1, NCF4, LITAF, SBD2, NFKB, TNF-α, IL1B, IL6, LGALS, and CATH1), antioxidant (SOD1, CAT, GPX1, GST, Nrf2, Keap1, HMOX1, and NQO1), and GIT health (CALB1, GT, and MUC2) genes in healthy and diarrheic lambs.ResultsVirulent genetic markers of pathogenic characteristics of E. coli (astA, Vt2e (Stx2e), CFA/I, groES and luxS) and Salmonella (invA, SopB, bcfC and avrA) were detected in all diarrheic lambs. PCR-DNA sequencing of immune, antioxidant and intestinal health genes found eleven single nucleotide polymorphisms (SNPs) linked to either diarrhea resistance or susceptibility in Barki lambs. Transcript levels of immune, antioxidant, and GIT health (CALB1, GT, and MUC2) genes varied between healthy and diarrheic lambs. Nucleotide sequence variation of the genes under inquiry between reference sequences in GenBank and those of the animals under investigation verified all identified SNPs. Significant (P = 0.001) erythrocytosis, neutrophilic leukocytosis, with lymphocytopenia were observed in diarrheic lambs. Significant (P = 0.001) increases in serum IL-1α, IL-1β, IL-6, TNF-α (90.5 ± 1.7, 101.8 ± 1.7, 72.3 ± 6.6, 71.26 ± 4.89 Pg/ml, respectively), serum Fb, Cp, Hp, SAA (230.7 ± 12.4 mg/dl, 6.5 ± 0.07 mg/dl, 2.5 ± 0.09 g/dl, 7.4 ± 0.4 mg/L, respectively), free radicals (MDA, NO), cortisol (6.91 ± 0.18 μg/dl) and growth hormone, with significant (P = 0.001) decreases in serum IL-10 (81.71 ± 1.05 Pg/ml), antioxidants (CAT, GPx), insulin, triiodothyronine (T3) and thyroxine (T4) in diarrheic lambs.ConclusionsThe study's findings provided credence to the theory that marker-assisted selection (MAS) could be used to predict and prevent diarrhea in Barki sheep by selecting lambs based on SNPs in genes linked to inflammation, antioxidants, and intestinal health. In order to establish an efficient management protocol and determine the most susceptible risk period for disease occurrence, gene expression profiles of the genes under investigation, pro-inflammatory cytokines and acute phase proteins may also be utilized as proxy biomarkers for lamb enteritis.

Synergistic interactions of biocontrol agents and chemical fungicides enhance the disease resistance in Vigna radiata (L.) against Macrophomina phaseolina-associated with dry root rot

Macrophomina phaseolina, a necrotrophic fungus responsible for dry root rot disease in Vigna radiata L. (greengram) causes extensive yield losses. Biocontrol agents are reported to suppress phytopathogens, mitigate biotic stress, and improve growth and yield of plants. Here, Bacillus subtilis PSB-5 and Trichoderma sp. TD-6 along with chemical fungicides; mancozeb (MZB) and carbendazim (CBZM) were evaluated alone/or in combination for their effectiveness against M. phaseolina-induced root rot disease in greengram. B. subtilis and Trichoderma sp. suppressed phyto-fungal growth by 72 and 78 %, respectively. Both bioagents synthesized indole-3-acetic acid, ammonia, and solubilized insoluble phosphate, released antimicrobial substances including siderophore, hydrogen cyanide, and various extracellular lytic enzymes. Further, efficacy of bioagents and fungicides (at 50 and 100 ppm) were tested (single and combined) against M. phaseolina-infected greengram cultivated in pot soils. While evaluating, bioagents and fungicides increased plant height, biomass, and vigor indices of infected greengram in order: PSB-5 + TD-6 > PSB-5 > TD-6 > MZB + CBZM (100 ppm) > CBZM (100 ppm) > MZB (100 ppm). Further, among treatment, dual inoculation of bioagents (B. subtilis + Trichoderma), maximally increased total chlorophyll (59.4 %), carotenoid (68 %), root phosphorous (69.6 %), root nitrogen (65.7 %), total soluble protein (80 %), soluble sugar (76 %), pod yield (82.3 %) and seed protein (68 %) over infected plants. Moreover, biotic stress-induced oxidative stress biomarkers (proline, malondialdehyde, electrolyte leakage) and reactive oxygen species were significantly (p ≤ 0.05) lowered in fungal-infected greengram following fungicides and bioagents application. Furthermore, combined inoculation of bioagents significantly (p ≤ 0.05) reduced percent disease index (PDI) and increased % protection in biotic-stressed greengram. Besides, bioagents potentially increased disease resistance in M. phaseolina-infected greengram plants by modulating defense responses such as activities of β-1, 3 glucanase, catalase, phenylalanine ammonia lyase, polyphenol oxidase, peroxidase, and superoxide dismutase which significantly protected plants from fungal pathogen. Soil populations of pathogen and bioagents declined and considerably increased, respectively, at harvest. Application of antagonistic bacterial and fungal strains enhances greengram resistance to M. phaseolina while concurrently offering agriculture an environmentally friendly choice. Also, these strains can be applied as biocontrol agents in disease suppression over chemical fungicides.

Unraveling Mitochondrial Reactive Oxygen Species Involvement in Psoriasis: The Promise of Antioxidant Therapies.

Psoriasis is a chronic inflammatory skin disorder characterized by immune dysregulation and aberrant keratinocyte proliferation. Despite tremendous advances in understanding its etiology, effective therapies that target its fundamental mechanisms remain necessary. Recent research highlights the role of reactive oxygen species dysregulation and mitochondrial dysfunction in psoriasis pathogenesis. Mitochondrial reactive oxygen species mediate cellular signaling pathways involved in psoriasis, such as proliferation, apoptosis, and inflammation, leading to oxidative stress, exacerbating inflammation and tissue damage if dysregulated. This review explores oxidative stress biomarkers and parameters in psoriasis, including myeloperoxidase, paraoxonase, sirtuins, superoxide dismutase, catalase, malondialdehyde, oxidative stress index, total oxidant status, and total antioxidant status. These markers provide insights into disease mechanisms and potential diagnostic and therapeutic targets. Modulating mitochondrial reactive oxygen species levels and enhancing antioxidant defenses can alleviate inflammation and oxidative damage, improving patient outcomes. Natural antioxidants like quercetin, curcumin, gingerol, resveratrol, and other antioxidants show promise as complementary treatments targeting oxidative stress and mitochondrial dysfunction. This review aims to guide the development of personalized therapeutic methods and diagnostic techniques, emphasizing the importance of comprehensive clinical studies to validate the efficacy and safety of these interventions, paving the way for more effective and holistic psoriasis care.

Exploring immunoglobulin A as a stress biomarker in lions (Panthera leo): Validation of an immunoassay for its measurement in feces

Immunoglobulin A (IgA) has been investigated as a stress biomarker with the potential to complement glucocorticoid measurements in welfare assessments. This study aimed to develop the methodology and validate an enzyme immunoassay (EIA) for quantifying IgA in feces (FIgA) of lions (Panthera leo), investigate excretion patterns of FIgA under baseline conditions in captive lions, and explore its relationship with fecal glucocorticoid metabolites (FGM). Feces were collected from 11 lions housed in stable social groups at four Spanish zoos over a period of two to six weeks. FIgA was reliably quantified using a commercial EIA, with concentrations ranging from 0.28 to 794.17 μg IgA/g feces, showing substantial intra- and inter-individual variability. Females had significantly higher FIgA concentrations than males (113.10 vs 54.96 μg IgA/g feces; p < 0.01). Additionally, FIgA concentrations varied across zoos (p < 0.001). Positive correlations were found between FIgA and FGM for all samples combined (rho = 0.43, p < 0.001) and across individual means (rho = 0.70, p < 0.05), but not consistently when examining each lion separately. This study demonstrates for the first time that IgA can be reliably quantified in lion feces, paving the way for its application in welfare studies.

Semen static oxidation-reduction potential is not helpful in evaluating male fertility.

Infertility affects a significant percentage of couples worldwide, with male infertility contributing substantially in a considerable number of cases. Research indicates that oxidative stress is a critical factor impacting male fertility. To explore the relationship between semen static oxidation-reduction potential (sORP), sperm parameters, and validated biomarkers of oxidative stress in infertile men. This cross-sectional study involved 202 men diagnosed with idiopathic male factor infertility and male partners from couples with unexplained infertility. Multivariable linear regression to query the associations between sORP, sperm parameters, and oxidative aggression biomarkers (lipid peroxidation, mitochondrial membrane potential, annexin V, and sperm DNA fragmentation). SORP has no linear association with any semen analysis parameter. Furthermore, its relationship with validated biomarkers of oxidative stress was inconsistent. sORP was inversely related to lipid peroxidation (multivariable linear regression coefficient: -0.64), positively associated with sperm DNA fragmentation (multivariable linear regression coefficient: 3.20), and unrelated to mitochondrial membrane potential or annexin V. There is no clear or consistent relationship between sORP and validated oxidative aggression biomarkers or sperm parameters. Our findings suggest that sORP is unlikely to be helpful in the evaluation of a male with idiopathic infertility.

Flexible Electromagnetic Sensor with Inkjet-Printed Silver Nanoparticles on PET Substrate for Chemical and Biomedical Applications.

For this article, a low-cost, compact, and flexible inkjet-printed electromagnetic sensor was investigated for its chemical and biomedical applications. The investigated sensor design was used to estimate variations in the concentration of chemicals (ethanol and methanol) and biochemicals (hydrocortisone-a chemical derivative of cortisol, a biomarker of stress and cardiovascular effects). The proposed design's sensitivity was further improved by carefully choosing the frequency range (0.5-4 GHz), so that the analyzed samples showed approximately linear variations in their dielectric properties. The dielectric properties were measured using a vector network analyzer (VNA) and an Agilent 85070E Dielectric Probe Kit. The sensor design had a resonant frequency at 2.2 GHz when investigated without samples, and a consistent shift in resonant frequency was observed, with variation in the concentrations of the investigated chemicals. The sensitivity of the designed sensor is decent and is comparable to its non-flexible counterparts. Furthermore, the simulation and measured results were in agreement and were comparable to similar investigated sensor prototypes based on non-flexible Rogers substrates (Rogers RO4003C) and Rogers Droid/RT 5880), demonstrating true potential for chemical, biomedical applications, and healthcare.

Cucurbitacin-E; Curvularia lunata Secondary Metabolite as a BRCA 1 and 2 Regulator in Mice Associated Breast Cancer

Background: Cucurbitacin-induced apoptosis and inhibition of cell growth can render several cancers ineffective. The microbial transformation of cucurbitacin-E-glucoside to cucurbitacin- E was carried out by Curvularia lunata (NRRL 2178). Moreover, in vitro anticancer activity against the MCF-7 cell line as well as in vivo anticancer activity against dimethylbenz (a) anthracene (DMBA)-induced breast cancer in mice using cucurbitacin-E was evaluated. Methods: The cucurbitacin-E-glucoside was biotransformed by Curvularia lunata to cucurbitacin- E, and the isolated compound was tested in vitro against the MCF-7 cell line, and its IC50 was calculated. LD50 of cucurbitacin-E was estimated in mice, and its protective activity against DMBA-induced cancer in mice was studied. Breast cancer induction was done by a single-dose subcutaneous administration of DMBA (50 mg). Plasma ALT, AST, ALP, and LDH, as well as GSH, SOD, GPx, MDA, TNF-α, IL-6, and tumor suppressor P53 assays, were used to assess cucurbitacin- E's capacity to protect the liver and breast against DMBA-induced toxicity. Moreover, by assessing the gene expression of tumor suppressor genes (BRCA 1 and 2) and conducting histopathological analysis, the suppressive effect of cucurbitacin-E was examined. Results: The IC50 value of cucurbitacin-E against MCF-7 cell lines equals 72.15 ± 0.64 μg/ml. LD50 of cucurbitacin-E given orally in adult mice is equal to 1200 mg/kg b.w. The levels of plasma ALT, AST, ALP, and LDH were decreased significantly in DMBA-treated mice when administered with cucurbitacin-E at 1/50 LD50 (24 mg/kg/b.w.) and 1/20 LD50 (60 mg/kg/b.w.). In breast tissue, the levels of GSH, SOD, GPx, and P53 were significantly increased, as were decreased levels of TNF-α, IL-6, P53, and MDA. Conversely, there was a downregulation in the mRNA expression levels of BRCA1 and BRCA2. The histopathological analysis revealed that cucurbitacin-E management improved the tissue architecture of breast tumors. Conclusions: These findings demonstrate the ability of cucurbitacin-E to inhibit cancer cells in the rat breast by controlling oxidative stress and inflammatory biomarkers, as well as downregulating the mRNA expression levels of BRCA1 and BRCA2.

Urinary L-FABP Assay in the Detection of Acute Kidney Injury following Haematopoietic Stem Cell Transplantation.

Background: Acute Kidney Injury (AKI) is a condition that affects a significant proportion of acutely unwell patients and is associated with a high mortality rate. Patients undergoing haemopoietic stem cell transplantation (HSCT) are in an extremely high group for AKI. Identifying a biomarker or panel of markers that can reliably identify at-risk individuals undergoing HSCT can potentially impact management and outcomes. Early identification of AKI can reduce its severity and improve prognosis. We evaluated the urinary Liver type fatty acid binding protein (L-FABP), a tubular stress and injury biomarker both as an ELISA and a point of care (POC) assay for AKI detection in HSCT. Methods: 85 patients that had undergone autologous and allogenic HSCT (35 and 50, respectively) had urinary L-FABP (uL-FABP) measured by means of a quantitative ELISA and a semi-quantitative POC at baseline, day 0 and 7 post-transplantation. Serum creatinine (SCr) was also measured at the same time. Patients were followed up for 30 days for the occurrence of AKI and up to 18 months for mortality. The sensitivity and specificity of uL-FABP as an AKI biomarker were evaluated and compared to the performance of sCr using ROC curve analysis and logistic regression. Results: 39% of participants developed AKI within 1 month of their transplantation. The incidence of AKI was higher in the allogenic group than in the autologous HTSC group (57% vs. 26%, p = 0.008) with the median time to AKI being 25 [range 9-30] days. This group was younger (median age 59 vs. 63, p < 0.001) with a lower percentage of multiple myeloma as the primary diagnosis (6% vs. 88%, p < 0.001). The median time to AKI diagnosis was 25 [range 9-30] days. uL-FABP (mcg/gCr) at baseline, day of transplant and on the 7th day post-transplant were 1.61, 5.39 and 10.27, respectively, for the allogenic group and 0.58, 4.36 and 5.14 for the autologous group. Both SCr and uL-FABP levels rose from baseline to day 7 post-transplantation, while the AUC for predicting AKI for baseline, day 0 and day 7 post-transplant was 0.54, 0.59 and 0.62 for SCr and for 0.49, 0.43 and 0.49 uL-FABP, respectively. Univariate logistic regression showed the risk of AKI to be increased in patients with allogenic HSCT (p = 0.004, 95%CI [0.1; 0.65]) and in those with impaired renal function at baseline (p = 0.01, 95%CI [0.02, 0.54]). The risk of AKI was also significantly associated with SCr levels on day 7 post-transplant (p = 0.03, 95%CI [1; 1.03]). Multivariate logistic regression showed the type of HSCT to be the strongest predictor of AKI at all time points, while SCr levels at days 0 and 7 also correlated with increased risk in the model that included uL-FABP levels at the corresponding time points. The POC device for uL-FABP measurement correlated with ELISA (p < 0.001, Spearman 'correlation' = 0.54) Conclusions: The urinary biomarker uL-FABP did not demonstrate an independent predictive value in the detection of AKI at all stages. The most powerful risk predictor of AKI in this setting appears to be allograft recipients and baseline renal impairment, highlighting the importance of clinical risk stratification. Urinary L-FAPB as a POC biomarker was comparable to ELISA, which provides an opportunity for simple and rapid testing. However, the utility of LFABP in AKI is unclear and needs further exploration. Whether screening through rapid testing of uL-FABP can prevent or reduce AKI severity is unknown and merits further studies.

Stress biomarker response in Aporrectodea caliginosa earthworms exposed to single and combined pesticide treatments (Prosaro and Decis).

This study aims to assess the impact of two pesticides commonly used in Algeria (Prosaro XRT and Decis 25 EC), as well as their combinations at recommended doses, on a non-target species bioindicator of soil pollution, the earthworm Aporrectodea caliginosa, using physiological (mortality and growth) and biochemical parameters (proteins, glutathione, catalase activity and glutathione S-transferase, acetylcholine esterase, lipoxygenase). The recommended dose and its double were tested individually and in combination for this. It should be noted that the protocol used and the initial concentrations selected are the same as those used in the field. After 7 and 14 days (7D/14D) of exposure, all dosages were administered. Our findings show that the pesticides tested had no effect on earthworm survival. However, a significant decrease in their growth rates depending on the different concentrations was observed for the different treatments over the entire exposure period of 7 or 14 D. The greatest reductions (31.62%, 35.04%) are reported after 14D for the high concentrations of Decis alone (D2) as well as for the combined treatment Prosaro/Decis (P2/D2). At the same time, an increase in total protein contents (more than 50% after 14D) as well as a decrease in acetylcholine esterase activity were reported for all treatments. We were also able to identify the induction of oxidative stress after xenobiotic exposure, which is more pronounced at the end of the treatment (14D), resulting in the stimulation of the antioxidant system (gluthione, glutathione S-transférase, catalase) as well as the induction of lipoxygenase, which is responsible for the oxidation of polyunsaturated fatty acids as well as the generation of reactive oxygen species (ROS) involved in the inflammatory phenomenon. Finally, it turns out that the species Aporrectodea caliginosa is sensitive to the different concentrations applied, even those used in the open field, and that Decis (deltamethrin) seems to be more toxic than Prosaro and that the combinaison P2/D2 is as toxic as Decis alone (D2).

Bioaccumulation potentials of per-and polyfluoroalkyl substances (PFAS) in recreational fisheries: Occurrence, health risk assessment and oxidative stress biomarkers in coastal Biscayne Bay

Per-and polyfluoroalkyl substances (PFAS) are a group of synthetic, highly fluorinated, and emerging chemicals that are reported to be used for both industrial and domestic applications. Several PFAS have demonstrated persistent, bioaccumulative and toxic tendencies in marine organisms. Therefore, this research aims to characterize and quantify these compounds in both recreational fisheries and surface water samples, including estimating their bioaccumulation potentials. In addition, we assessed the potential contribution of biomonitoring tools such as oxidative stressors and morphological index on fish and ecological health. Finally, human health risk assessment was performed based on available toxicological data on limited PFAS. All PFAS were detected in at least one sample except for N-EtFOSAA in lobster which was below the method detection limit. ƩPFAS body burden ranged from 0.15 to 3.40 ng/g wet weight (ww) in blackfin tuna samples and 0.37–5.15 ng/g ww in lobster samples, respectively. Wilcoxon rank paired test (α = 0.05) shows that there is statistical significance (ρ < 0.05) of ƩPFAS between species. Bioaccumulation factors (BAF) suggest an increasing trend in PFAS classes (PFCAs < PFSAs < FTSs), with higher BAFs observed in tuna compared to lobster. Long-chain PFESAs and FASAA were reported at higher concentrations in lobster compared to Blackfin tuna due to their bioavailability through sediment-sorption interactions. Although Fulton’s condition factor (FCF) indicates healthy fish conditions, oxidative stress biomarkers suggest that tuna and lobster might be under stress, which can weaken their immune system against exposure to emerging contaminants such as PFAS. Hazard risk (HR) suggests a low risk to human health based on the consumption of the studied species; however, the risk of contaminant exposure may be higher than estimated. This study is aimed at improving food safety by providing better understanding of how PFAS infiltrate into human diet and incorporating data on influence of contaminant exposure and environmental stressors on marine health.

18F]FDG Brain Imaging Assessment in Preclinical Acute and Chronic Stress Models Using Statistical Parametric Mapping

Previous studies have used [18F]FDG as a biomarker for depression, anxiety, or chronic stress in cancer patients1,2. However, they lack specific brain patterns and assessment in preclinical models, limiting their translational potential. Hence, we set out to establish preclinical [18F]FDG brain PET as a method to evaluate stress in vivo. Lean C57BL/6J mice were exposed to acute and chronic cooling, restraint, and surgical stress. Obese mice were on a high-fat diet for eight weeks and exposed to cooling and restraint stress. [18F]FDG was injected into fasted animals under brief isoflurane anesthesia via the tail vein. Following a 60-minute distribution phase during acute stress or one day after stress exposure (chronic), animals underwent static μPET/CT scans (Siemens® Inveon). Brain images were spatially normalized, and intensity normalization was performed using proportional and histogram-based scaling3 with PMOD (V. 3.8). Normalized images were analyzed using a brain atlas (M. Mirrione) to extract regional SUV and statistical parametric mapping (SPM12) for voxel-wise comparison. Overall, in lean mice, total brain [18F]FDG-uptake was significantly reduced across all stress models except for acute restraint, whereas total uptake was unaffected in obese mice. Subsequent brain atlas analysis of lean mice revealed changes in regional uptake for all stressors except for chronic cooling, while obese mice were affected by only acute and chronic restraint. Using SPM, we validated stress-specific hypo- and hypermetabolic areas in the brains of lean mice upon acute cooling, acute and chronic restraint, and surgery and in obese mice after chronic restraint (see Figure). We also identified overlapping areas in the brain stem and hypothalamus region following acute cooling and surgery, possibly due to post-surgical hypothermia. Our findings show that static [18F]FDG-imaging is a valuable tool for noninvasively assessing brain activity in a multitude of stress models and a suitable translational tool for stress research in mice. Please click on the 'PDF' for the full abstract!