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Objective: Neuroinflammation is involved in the pathology of Alzheimer’s disease (AD). Peripheral levels of various inflammatory cytokines are altered during AD pathogenesis. This study aimed to examine the role of peripheral inflammation in AD pathogenesis by measuring serum levels and gene expression of specific inflammatory cytokines in AD patients. Therefore, we analyzed serum interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-β1) levels and mRNA expressions of IL-6 and tumor necrosis factor-alpha (TNF-α) in peripheral blood mononuclear cells of AD patients and controls. Materials and Methods: We quantitatively assessed serum IL-6 and TGF-β1 levels in 25 AD patients and 33 age-matched controls using enzymelinked immunosorbent assay. In addition, we evaluated the mRNA expressions of IL-6 and TNF-α in peripheral blood mononuclear cells from 31 AD patients and their respective controls (n=30) via quantitative real-time polymerase chain reaction. Results: AD patients tended to have higher serum IL-6 and TGF-β1 levels compared to the controls, but the difference was not statistically significant. IL-6 and TNF-α mRNA expression was significantly downregulated in AD patients compared to the controls (p=0.000 and p=0.004; respectively). Serum IL-6 and TGF-β1 levels were negatively correlated with age in AD patients (p=0.025, r=-0.467 and p=0.035, r=-0.431; respectively). Conclusion: The outcomes of this study suggest a disruption in the peripheral immune response in individuals with AD. The observed decreased expression of cytokine genes in peripheral leukocytes may indicate a contributory mechanism through which peripheral cytokines influence AD pathogenesis. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a serious global health problem, and chronic HBV infection significantly increases the risk of liver fibrosis, cirrhosis, and even hepatocellular carcinoma in patients. Current first-line therapeutics such as nucleos(t)ide analogues and interferons are unable to completely clear cccDNA, so the vast majority of patients need to take long-term or even lifelong medication. However, long-term virological and biochemical responses can be achieved in some patients after drug withdrawal. Successfully screening these patients with drug withdrawal advantages is difficult. Hepatitis-B-core-related antigen (HBcrAg) is a new HBV serological marker that which can reflect the level and transcription activity of cccDNA in hepatocytes. Therefore, HBcrAg has potential value in guiding patients in drug withdrawal. This review summarizes previous reports on HBcrAg and evaluates the application value of HBcrAg in safe drug discontinuation. [ABSTRACT FROM AUTHOR]

Cell division cycle 42 (CDC42) regulates cholesterol efflux, chronic inflammation, and reendothelialization in various atherosclerotic diseases. This study aimed to investigate the correlation of serum CDC42 with myocardial injury indicators and major adverse cardiac event (MACE) in ST-elevation myocardial infarction (STEMI) patients who were treated with percutaneous coronary intervention (PCI). In 250 STEMI patients about to receive PCI, serum samples were collected at enrollment before PCI treatment, and the serum samples were also obtained from 100 healthy controls (HCs) at enrollment. Serum CDC42 was detected by enzyme-linked immunosorbent assay. Serum CDC42 was decreased (versus HCs, P < 0.001) and negatively correlated with diabetes mellitus (P = 0.017), multivessel disease (P = 0.016), cardiac troponin I (P < 0.001), creatine kinase MB (P = 0.012), stent diameter ≥ 3.5 mm (P = 0.039), white blood cell (P < 0.001), low-density lipoprotein cholesterol (P = 0.049), and C-reactive protein (P < 0.001) in STEMI patients. Besides, 29 (11.6%) STEMI patients experienced MACE. The 1-year, 2-year, and 3-year accumulating MACE rates were 7.5%, 17.3%, and 19.3%, accordingly. Serum CDC42 was reduced in STEMI patients who experienced MACE compared to those who did not (P = 0.001). Serum CDC42 ≥ 250 pg/mL, ≥ 400 pg/mL, ≥ 700 pg/mL (cut by near integer value of 1/4th quartile, median, and 3/4th quartile) were associated with decreased accumulating MACE rates in STEMI patients (all P < 0.050). Notably, serum CDC42 ≥ 250 pg/mL (hazard ratio = 0.435, P = 0.031) was independently related to reduced accumulating MACE risk in STEMI patients. A serum CDC42 level of ≥ 250 pg/mL well predicts decreased MACE risk in STEMI patients who are treated with PCI. [ABSTRACT FROM AUTHOR]

Background: A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease. Aims: Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients. Methods: The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction. Results: We identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956–0.987) and 0.924 (95% CI 0.899–0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%. Conclusions: A panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic. [ABSTRACT FROM AUTHOR]

The objectives of this study were to compare the serum and seminal plasma pharmacokinetic profiles of florfenicol (FLO) and florfenicol amine (FLA) after the administration of FLO either by IM or SC routes in beef bulls. Four clinically healthy Hereford bulls underwent a comprehensive physical exam, including breeding soundness examination, CBC, and chemistry profile panel. Bulls were healthy and classified satisfactory potential breeders. In one group (n = 2), a single dose of FLO was administered SC in the middle of the neck at a dose of 40 mg/kg of body weight. In the second group (n = 2), a single dose was administered IM in the muscles of the neck at a dose of 20 mg/kg. Concentrations of FLO and FLA in serum and seminal plasma were determined by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Blood and semen samples were collected before the administration of FLO and at 12, 24, 36, 48, 72, 96, 120, 144, and 168 h after injection. The blood was collected from the coccygeal vessels, and semen was collected by electroejaculation. All samples were immediately refrigerated, processed within the first hour after collection, and finally stored at −80 °C. The mean level of total FLO in serum was higher when administered by the SC route (1,415.5 ng/mL) than by the IM route (752.4 ng/mL; P = 0.001). Differences were observed between the percentage of FLA in serum (1.8%; ranging from 1.3 to 2.9) and in seminal plasma (27.5%; ranging from 15.9 to 34.2; P = 0.0001). The mean level (±SD) of FLA was higher in seminal plasma compared to serum (467 ± 466 ng/mL and 18 ± 16 ng/mL, respectively; P = 0.001). The mean level of total FLO in seminal plasma was 1,454.8 ng/mL for the SC route and 1,872.9 ng/mL for the IM route without differences between the two routes (P = 0.51). Differences in the mean level of total FLO between serum and seminal plasma were detected (1,187 ± 2,069 ng/mL and 1,748 ± 1,906 ng/mL, respectively; P = 0.04). From the present investigation, it was concluded that FLO is a suitable antibiotic based on its pharmacokinetic attributes and may be employed for the treatment of bull genital infections when its use is indicated. To study the pharmacokinetics of FLO in seminal plasma, the analysis of FLA should be incorporated. [ABSTRACT FROM AUTHOR]

Various activities in chemical stores such as production, packaging, repackaging, offloading, and storing of chemicals can emit toxic chemicals into the ambient air which may be detrimental to health. This research work aimed to determine whether or not there is hepatoxicity and nephrotoxicity in chemical storekeepers. A total of twenty male adult storekeepers of four chemical stores were used as subjects. Four male storekeepers of a garment store 1km from the chemical stores of the same market were used as control subjects. Heavy metals in the indoor air of the shops and the blood samples of the subjects were determined using an atomic absorption spectrophotometer while an aerocet analyzer was used for the measurement of particulate matter. Kidney and liver function tests were carried out on the serum of subjects using standard analytical test kits. Concentrations of all the assayed heavy metals in the ambient air of the chemical stores and the blood samples of chemical storekeepers were significantly higher (p<0.05) than in the controls. Particulate matter concentrations in all the chemical stores increased significantly (p<0.05). Serum urea, creatinine, sodium ion, potassium ion, chloride, and bicarbonate were significantly elevated (p<0.05) in the chemical storekeepers compared to control subjects. Concentrations of serum bilirubin and liver enzymes were significantly elevated (p<0.05) while total protein and albumin concentrations were significantly decreased (p<0.05) in the majority of the chemical storekeepers compared to the control subjects. There were strong indications of renal and hepato-toxicities in the chemical storekeepers at Ariaria International Market. [ABSTRACT FROM AUTHOR]

To determine the pharmacokinetics (PK), safety, and bioequivalence profiles of 0.5‐g calcium dobesilate capsules in both fasting and fed states for the test drug and reference drug. A randomized‐sequence, single‐dose, open‐label, 2‐period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR202000268‐01). The fasting and fed studies, both involving 24 subjects, were conducted. A single dosage of either the reference or the test preparation was given to each eligible subject in a 1:1 ratio, followed by a 7‐day rest interval before the administration of the alternative formulation. After taking the capsules, plasma samples were taken for 48 hours, and using liquid chromatography‐tandem mass spectrometry, the calcium dobesilate level was determined. The PK parameters evaluated in the study included the maximum serum concentration (Cmax), area under the plasma concentration‐time curve (AUC) from time 0 to the last quantifiable concentration, AUC from time 0 to infinity, half‐life, time to Cmax, and terminal elimination rate constant. In addition, the safety evaluation encompassed monitoring fluctuations in vitals (temperature, pulse, and blood pressure) and laboratory tests (urinalysis, hepatic function, blood biochemistry, and hematology), as well as recording the emergence of adverse events (AEs). The geometric mean ratio (GMR) of the test/reference medications was used to assess bioequivalence by determining if the 90% confidence intervals of the GMR fell within the predefined range of 80%‐125%. AEs were assessed as safety end points. The study included 48 healthy Chinese volunteers (with n = 24 each for the fasting and the fed conditions), and no subjects dropped out for any reason. The differences in the PK metrics for the test and reference drugs for both conditions were insignificant (P >.05). For bioequivalence, irrespective of whether the food was consumed or not, the range of the 90% confidence intervals of the GMR for Cmax, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity was between 80% and 125%. In the experiment, no serious AEs were recorded. Our findings revealed that the calcium dobesilate capsules used as the reference and the test drugs were both bioequivalent. Irrespective of whether the healthy Chinese volunteers consumed food or not, the PK and safety profiles were comparable. [ABSTRACT FROM AUTHOR]

Congenital anomalies of the kidney and urinary tract are collectively one of the most commonly diagnosed antenatal conditions. Clinicians have several tools available to diagnose anomalies, including imaging, biomarkers, family history and genetic studies. In certain cases, antenatal interventions such as vesico-amniotic shunting may be considered to improve postnatal outcomes. Congenital kidney anomalies detected antenatally can vary in clinical significance from almost no impact postnatally to significant morbidity and perinatal mortality. Prognosis broadly depends on kidney size, structure and amount of amniotic fluid, alongside genetics and family history, and progression on subsequent scans. It is important to counsel parents appropriately using a parent-focused and personalised approach. The use of a multidisciplinary team should always be considered. [ABSTRACT FROM AUTHOR]

Objective: The aim was to profile serum and salivary levels of active‐matrix metalloproteinase (aMMP)‐8, tissue inhibitor MMP (TIMP)‐1, aMMP‐8/TIMP‐1 ratio, total MMP (tMMP)‐9, tMMP‐9/TIMP‐1 ratio, myeloperoxidase (MPO), and human neutrophil elastase (HNE) in periodontitis and rheumatoid arthritis (RA). Materials and Methods: Rheumatoid arthritis patients with periodontitis (RA + P, n = 26), periodontally healthy RA patients (RA, n = 23), systemically healthy periodontitis patients (P, n = 24), and controls (C, n = 24) were included. aMMP‐8 levels were determined by a time‐resolved immunofluorescence assay (IFMA), TIMP‐1, tMMP‐9, MPO, and HNE levels were measured by enzyme‐linked immunosorbent (ELISA) assays. Results: Higher salivary aMMP‐8 (p < 0.001), aMMP‐8/TIMP‐1 ratio (p = 0.043), tMMP‐9 (p = 0.011), tMMP‐9/TIMP‐1 ratio (p = 0.022), MPO (p = 0.026) and HNE (p < 0.001) levels were detected in P relative to the controls. Salivary TIMP‐1 was increased in RA patients regardless of periodontal status (RA + P vs. P: p = 0.038; RA vs. C: p = 0.020). Serum neutrophil proteases were increased in RA groups (RA + P, RA) compared to systemically healthy groups (P, C) (p < 0.05). Conclusions: Serum levels of neutrophil proteases were increased in RA study groups; however rheumatologic status seemingly does not affect salivary levels of these proteins. [ABSTRACT FROM AUTHOR]

In this study, 1811 serum samples of 1764 patients who applied to the parasitology laboratory of Gaziantep Dr. Ersin Arslan Training and Research Hospital between 1 January 2015 and 31 December 2022 with preliminary diagnosis of cystic echinococcosis (CE) were investigated, in order to evaluate the demographic data of the patients and CE seropositivity on an annual base. 1811 serum samples were analyzed by ELI.H.A Echinococcus ELITech (MICROBIO, France) test which is based on the indirect haemagglutination principle. Seropositivity was detected in a total of 519 patients. Of the patients who were found to be positive, 341 were women and 178 were men. The highest positivity rate was found in patients over 50 years of age (29.3%), followed by the 20-30 age group (23.1%) and the 30-40 age group (22.9%), respectively. While 232 of the admitted patients with preliminary diagnosis of CE were Syrians, 1532 patients were Turkish citizens. The positivity rate in Syrian patients was determined to be 41.8%, (n=100) while this rate was 26.7% (n=419) in Turkish patients. Despite the developments in the socioeconomic field, the investments of local governments in sanitation and the establishment of single health awareness, CE continues to exist as an important public health problem in Gaziantep due to both the effect of migration and the inability to reach the desired levels of personal hygiene. [ABSTRACT FROM AUTHOR]

The effect of treatment by zoledronic acid combined with exemestane was explored pertaining to the immune function, sex hormones, bone markers, and clinical efficacy in hormone receptor-positive breast cancer patients. Eighty elderly patients with hormone receptor-positive breast cancer were selected as the study subjects who were clinically admitted from December 2016 to December 2021. The study and control groups had 40 cases each and were analyzed according to different treatment methods. The control group received exemestane treatment, while the study group was treated with a combination of zoledronic acid and exemestane. The immune functions, sex hormones, bone markers, clinical efficacy, adverse reactions, life quality scores, serum calcium, and vascular endothelial growth factor for the two groups were analyzed and compared. The cluster of differentiation (CD), E2, P and T levels were lower than those of the control after treatment, and the difference was statistically significant, p < 0.05. Similar effect was observed in β-Cross Laps, serum calcium levels and N-terminal propeptide of type 1precollagen (PINP) levels. Physiological and psychological scores were higher than the control after treatment, and difference was statistically significant, p < 0.05. The incidence of adverse reactions was 20.00% for the study group while 42.50% for control, and the difference was statistically significant, p < 0.05. We conclude that Zoledronic acid combined with exemestane in treating hormone receptor-positive breast cancer patients could improve clinical efficacy, immune function, bone metabolism, quality of life, regulate the sex hormones, and possess drug safety. [ABSTRACT FROM AUTHOR]

Objective • To observe the levels of serum 3-nitrotyrosine (3-NT), neuronal PAS domain protein 4 (NPASDP-4), and S100β protein in patients diagnosed with cerebral infarction and analyze their correlation with cognitive dysfunction in these patients. Methods • The study included a cohort of 158 patients suffering from cerebral infarction who were admitted to the Liwan District Hospital of Traditional Chinese Medicine between January 2021 and December 2022. After stabilizing vital signs, all patients underwent the Montreal Cognitive Assessment (MoCA) to assess their cognitive function. Based on the assessment results, they were divided into two groups: the cognitive dysfunction group (121 cases) and the normal cognitive function group (37 cases). The baseline characteristics and serum levels of 3-NT, neuronal PAS domain protein 4 (NPASDP-4), and S100β protein were compared in the patient cohorts. Furthermore, the correlation between these three indicators and cognitive function in patients suffering from cerebral infarction was analyzed. A logistic regression model was constructed to analyze how serum levels of 3-NT, NPASDP-4, and S100β protein levels affected cognitive function in patients suffering from cerebral infarction. ROC curve analysis was conducted to assess the predictive value of serum 3-NT, NPASDP-4, and S100β protein levels for cognitive function in patients suffering from cerebral infarction. Results • Among the 158 patients with cerebral infarction, 121 (76.58%) had cognitive dysfunction, while 37 (23.42%) had normal cognitive function. The levels of 3-NT, NPASDP-4, and S100β protein were found to be significantly higher in the cognitive dysfunction group compared to the normal cognitive function group (t = 5.788, 7.774, 6.460; P = .000, .000, .000). The point-biserial correlation analysis results showed a positive correlation between serum levels of 3-NT, NPASDP-4, and S100β protein and the occurrence of cognitive dysfunction in patients suffering from cerebral infarction (r=0.420, 0.529, 0.424; P = .000, .000, .000). The logistic regression model demonstrated that serum levels of 3-NT(95%CI: 1.299-2.603), NPASDP-4(95%CI: 1.487-3.386), and S100β protein(95%CI: 1.153-8.746) were risk factors for cognitive dysfunction in patients suffering from cerebral infarction (OR=1.839, 2.244, 1.429; P = .001, .000, .240). ROC curve analysis demonstrated that serum 3-NT, NPASDP-4, and S100β protein levels exhibited a certain predictive value for cognitive function in patients with cerebral infarction (AUC = 0.789, 0.881, 0.820). Conclusion • Serum levels of 3-NT, NPASDP-4, and S100β protein are closely related to the cognitive function of patients with cerebral infarction, and abnormal changes in these levels may exacerbate cognitive dysfunction in these patients. [ABSTRACT FROM AUTHOR]

A small fraction of people vaccinated with mRNA–lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech's Comirnaty and Moderna's Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway. Control PEGylated liposomes (Doxebo) also induced C activation, but, on a weight basis, it was ~5 times less effective than that of Comirnaty. Viral or synthetic naked mRNAs had no C-activating effects. In peripheral blood mononuclear cell (PBMC) cultures supplemented with 20% autologous serum, besides C activation, Comirnaty induced the secretion of proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1β < TNF-α < IL-6 < IL-8. Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1β, and TNF-α, suggesting C-dependence of these cytokines' induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or other anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are often linked to ageing and are the major cause of death worldwide. The declined proliferation of adult stem cells in the heart often impedes its regenerative potential. Thus, an investigation of the proliferative potential of adult human cardiac stem cells (hCSCs) might be of great interest for improving cell-based treatments of cardiovascular diseases. The application of human blood serum was already shown to enhance hCSC proliferation and reduce senescence. Here, the underlying signalling pathways of serum-mediated hCSC proliferation were studied. We are the first to demonstrate the involvement of the transcription factor NF-κB in the serum-mediated proliferative response of hCSCs by utilizing the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). RNA-Sequencing (RNA-Seq) revealed ATF6B, COX5B, and TNFRSF14 as potential targets of NF-κB that are involved in serum-induced hCSC proliferation. [ABSTRACT FROM AUTHOR]

Introduction: The perception of hunger is a complex physiological process that requires precise coordination between the central and peripheral tissues. Methods: In this study, tilapia fasted for 24 h was chosen to establish a hunger model to study the mechanism of homeostasis recovery under the joint regulation of the central nervous system (CNS) and peripheral tissues. Results: The gastric and intestinal contents of tilapia were predominantly depleted after a fasting period of 9 h and 24 h, respectively. The serum glucose level significantly decreased at the 9-h and 24-h fasting, respectively, and the glucokinase-dependent glucosensing mechanism in the liver was identified as well as the significant activation of phospho-AMPK. However, fasting for 24 h did not activate glucosensing mechanisms and AMPK signaling pathways in the hypothalamus. On the other hand, significant reductions were observed in the mRNA levels of the lipid synthesis-related genes fas and accα, and the serum triglyceride levels as well. The mRNA levels of npy, agrp, pomc, and cart in the hypothalamus fluctuated during the fasting period without significant differences. With in situ hybridization npy signals upregulated in the ventral zone of posterior periventricular nucleus after 24-h fasting, pomc signals enhanced in the lateral tuberal nucleus. Based on the serum metabolomic analysis, the levels of branched-chain amino acids, butyrate, and short-chain acylcarnitine decreased, while those of medium- and long-chain acylcarnitine increased. Conclusion: Fasting for 24 h resulted in changes in npy and pomc signals within the hypothalamus and triggered the glucosensing mechanism in the liver of tilapia. This study is beneficial for elucidating the response of neuropeptides in the CNS to the changes of nutritional factors when hungry. [ABSTRACT FROM AUTHOR]

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. Methods: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. Results: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13–21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54–93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79–88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. Conclusion: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease, resulting from chronic alcohol use, includes conditions like fatty liver, alcoholic hepatitis, and cirrhosis. This study assessed TNF-α and leptin levels in 45 alcoholic liver disease patients, explored their relationship, and examined the rs1137101 polymorphism in the leptin receptor gene. Participants (mean age 40.13 ± 10.36) had consumed alcohol for an average of 15.31 ± 9.49 years at a daily intake of 253.33 ± 118.25 mL. TNF-α increased with age, while no age-leptin correlation was observed. TNF-α and leptin showed a negative correlation. The study identified a 48% minor allele G frequency for rs1137101. The findings highlight a significant correlation between TNF-α and leptin levels in alcoholic liver disease, suggesting potential roles as inflammatory mediators. More prospective studies are needed to enhance our understanding of these factors and improve disease management, potentially reducing morbidity and mortality rates. [ABSTRACT FROM AUTHOR]

Background: Prior studies suggest that physical activity lowers circulating C-reactive protein (CRP) levels. However, little is known about the association between regular active commuting, i.e. walking or cycling to work, and CRP concentrations. This study examines whether active commuting is associated with lower CRP. Methods: We conducted a cross-sectional study using population-based FINRISK data from 1997, 2002, 2007 and 2012. Participants were working adults living in Finland (n = 6208; mean age = 44 years; 53.6% women). We used linear and additive models adjusted for potential confounders to analyze whether daily active commuting, defined as the time spent walking or cycling to work, was associated with lower high-sensitivity (hs-) CRP serum concentrations compared with passive commuting. Results: We observed that daily active commuting for 45 min or more (vs. none) was associated with lower hs-CRP [% mean difference in the main model: -16.8%; 95% confidence interval (CI) -25.6% to -7.0%), and results were robust to adjustment for leisure-time and occupational physical activity, as well as diet. Similarly, active commuting for 15-29 min daily was associated with lower hs-CRP in the main model (-7.4; 95% CI -14.1 to -0.2), but the association attenuated to null after further adjustments. In subgroup analyses, associations were only observed for women. Conclusions: Active commuting for at least 45 min a day was associated with lower levels of low-grade inflammation. Promoting active modes of transport may lead not only to reduced emissions from motorized traffic but also to population-level health benefits. [ABSTRACT FROM AUTHOR]

Background: Toxocariasis is a zoonotic disease caused by the larvae of Toxocara canis or Toxocara cati. Patients with schizophrenia may be at higher risk of infection, possibly due to their cognitive and personal self-care impairments. We aimed to assess the association between Toxocara spp. exposure and schizophrenia. Methods: This case-control study was conducted on 109 patients with schizophrenia admitted to Ibn Sina Hospital, Shiraz, Iran, and 104 age- and gender-matched healthy controls from May to September 2021. A questionnaire was obtained and serum samples were tested for IgG antibodies to Toxocara excretory/secretory (TES) antigens using an enzyme-linked immunosorbent assay (ELISA). Results: Anti-Toxocara IgG was detected in 12 schizophrenic patients and 10 control subjects, giving respective seroprevalences of 11.0% (95% confidence interval [95% CI]=5.8-18.4%) and 9.6% (95% CI=4.7-17.0%). Univariate logistic analyses estimated an odds ratio (OR) of 1.16 (95% CI=0.44-3.16); however, it was not statistically significant (P=0.915). Individuals with a history of eating unwashed vegetables or fruits (23.1%, 95% CI=9.0-43.6, crude odds ratio [COR]=3.21, 95% CI=1.13-9.13) and rural residency (19.5%, 95% CI=8.8-34.9, COR=2.74, 95% CI=1.06-7.05) had significantly higher rates of seropositivity using the univariate logistic analyses. After multivariate logistic analyses, the differences were not statistically significant. Conclusion: The toxocariasis seroprevalence among schizophrenic and healthy participants was not significantly different (11% vs. 9.6%). Since the disease severity, onset, and cognitive sequelae are not the same among schizophrenic patients, clinically matched studies with larger samples are required to address the current inconsistency between the studies. [ABSTRACT FROM AUTHOR]

The aim of this study was to devise an algorithm that would predict flow cytometry crossmatch (FCXM) results using single‐antigen bead (SAB) mean fluorescent intensity (MFI) levels using samples received through the National External Quality Assurance Scheme (NEQAS) 2B external proficiency testing scheme between 2019 and 2023. A total of 159 serum samples were retrospectively screened using LABScreen Single Antigen Class I and II (SAB), and 40 peripheral blood samples were human leucocyte antigen (HLA) typed with LABType SSO. Donor‐specific antibodies were identified for each cell–serum combination tested, and cumulative MFI values were calculated for each test before correlating the screening result with the consensus crossmatch results for this scheme. HLA Class I MFIs were combined to predict the T cell crossmatch. For the B cell crossmatch prediction, two options were considered: (i) HLA Class II MFI values alone and (ii) HLA Class I + Class II MFIs. Receiver operating characteristic analysis was carried out to identify the combined MFI threshold that predicted NEQAS consensus results with the greatest sensitivity and specificity. HLA Class I combined MFI >5000 predicted T cell crossmatch results with 96% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 92% negative predictive value (NPV). For B cell results, HLA Class I + Class II combined MFIs >11,000 gave the best model, showing 97% sensitivity, 82% specificity, 96% PPV and 85% NPV. However, for samples with only HLA Class II sensitization, combined MFIs >13,000 improved the B cell crossmatch predictions: 92% sensitivity, 95% specificity, 96% PPV and 91% NPV. Using this model, combined MFI can be used to predict the immunological risk posed by donor‐specific antibodies when it is not possible to carry out an FCXM. [ABSTRACT FROM AUTHOR]

Background: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post‐injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non‐neuronal markers or pan‐neuronal markers with constitutive expressions. Methods: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA‐sequencing and qRT‐PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme‐linked immune‐sorbent assay (ELISA) kits. Results: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. Conclusions: ATF3 is an easily measurable, neuron‐specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. Highlights: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively.Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke.ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Sodium zirconium cyclosilicate (SZC) is an approved oral treatment for hyperkalemia that selectively binds potassium (K+) in the gastrointestinal tract and removes K+ from the body through increased fecal excretion. Here, we describe the population pharmacodynamic (PopPD) response of serum K+ concentration in patients with hyperkalemia who are treated with SZC, estimate the impact of patients' intrinsic and extrinsic factors, and compare predicted serum K+ responses between 5 g alternate daily (QOD) and 2.5 g once daily (QD) maintenance doses. Methods: PopPD analysis was based on pooled data from seven phase II and III clinical trials for SZC. A semi-mechanistic longitudinal mixed-effects (base) model was used to characterize serum K+ concentration after SZC dosing. Indirect-response, virtual pharmacokinetics–pharmacodynamics (PK–PD) modeling was used to mimic the drug exposure compartment. Full covariate modeling was used to assess covariate impact on the half-maximal effective concentration of drug (EC50), placebo response, and Kout. Models were evaluated using goodness-of-fit plots, relative standard errors, and visual predictive checks, and data were stratified to optimize model performance across subgroups. Covariate effects were evaluated based on the magnitude of change in serum K+ between baseline and end of correction phase dosing (48 h, SZC 10 g three times a day) and maintenance phase dosing (28 days, SZC 10 g QD) using a reference subject. Results: The analysis data set included 2369 patients and 25,764 serum K+ observations. The mean (standard deviation) patient age was 66.0 (12) years, 61% were male, 68% were White, 34% had congestive heart failure, and 62% had diabetes. Mean (standard deviation) serum K+ at baseline was 5.49 (0.43) mmol/L. Both the base and full covariance models adequately described observed data. In the final model, there was a sigmoid exposure response on Kin, with EC50 of 32.8 g and a Hill coefficient of 1.36. The predicted placebo-adjusted dose–responses of serum K+ change appeared nearly linear in the correction and maintenance phases. No clinically meaningful difference in placebo-adjusted serum K+ change from baseline at 28 days was observed between maintenance regimens of SZC 5 g QOD and 2.5 g QD. A greater SZC treatment response was associated with high serum K+ at baseline, advanced age, lower body weight, lower estimated glomerular filtration rate, and Black/African American and Asian race, compared with the reference patient. The impact of heart failure status and diabetes status was only minor. Conclusions: The PopPD model of SZC adequately described changes in serum K+ concentration during correction and maintenance phase dosing. A greater treatment response was associated with various covariates, but the impact of each was modest. Overall, these findings suggest that no adjustment in SZC dose is needed for any of the covariates evaluated. [ABSTRACT FROM AUTHOR]

Objectives Jaundice occurs in 60% of full-term and 80% of pre-term newborns. This study compared the effect of phototherapy with and without phenobarbital on icteric newborns. Materials & Methods This study is a randomized clinical trial conducted from July until March 2018 at Imam Reza Hospital, Mashhad University of Medical Science, Iran. Full-term and near-term neonates with more than 2000 grams who were hospitalized in the mentioned period for jaundice were entered into the study. The newborns were divided into two groups using block randomization. Data were analyzed by SPSS version 19. Results The average gestational age was 36.4 weeks (SD 2.39) in the intervention group and 36.9 weeks (SD 2.16) in the control group, with no significant difference between them. The mean hospital stay for the intervention group was 72 hours (SD 1.66), compared to 55 hours (SD 1.88) for the control group. At discharge, the serum bilirubin level in the intervention group was 11.53 mg/dL (SD 0.77), while it was 10.80 mg/dL (SD 1.09) in the control group, a statistically significant difference. Conclusion According to this study, phototherapy with phenobarbital is not more effective than phototherapy alone in neonatal hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Mesoporous carbon (MC) with a large surface area was developed to mix with the conventional carbon paste (CP) electrode. The developed MC/CP sensor had the highest sensitivity compared to many sensors made from other materials. A common drug, nitazoxanide (NTZ), was used as an application example. Using the MC/CP electrode and square wave-adsorptive stripping voltammetry (SW-AdSV), the concentration of NTZ in human serum was quantitatively estimated. We achieved a limit of quantification (LOQ) of 22 nM. [ABSTRACT FROM AUTHOR]

Compelling evidence indicates that dyslipidemia is positively associated with oral lichen planus (OLP). The types and magnitude of lipid metabolism disturbance in peripheral blood of OLP patients have been investigated in different studies. Yet, consensus on how these different lipid components varied in levels for the development of OLP lesions has not been reached so far. Herein, a total of 8 eligible studies were recognized, which enrolled 533 cases of OLP and 499 healthy controls. The analysis showed that the average total triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels were considerably higher, and high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in OLP patients compared to healthy controls. Collectively, the lipid profile panel maybe serve as the potential predictive indicator for screening OLP. [ABSTRACT FROM AUTHOR]

The pathophysiology of burning mouth syndrome (BMS), although considered a multifactorial etiology including psychological factors, is still not well understood. Hence, this study aimed to investigate the potential usage of salivary and serum biomarkers, including brain-derived neurotrophic factor (BDNF), interferon-gamma (IFN-γ), interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α), in diagnosing BMS and their correlations with anxiety/depression. 45 BMS patients and 14 healthy volunteers were enrolled. The patients were divided into BMS with anxiety/depression group and BMS without anxiety/depression group according to the scores of the Zung Self-rating Anxiety Scale (SAS) and Zung Self-rating Depression Scale (SDS). Additionally, concentrations of BDNF, IFN-γ, IL-1β, IL-6, IL-8, and TNF-α in saliva and those in serum among the patients and healthy volunteers were assessed by multiplex assay using Luminex 200TM system and Enzyme-linked immunosorbent assay (ELISA), respectively. Among all the serum biomarkers, only BDNF showed a statistically significant decrease in the patients than the healthy volunteers (P < 0.05). Regarding saliva biomarkers, BDNF, IL-1β, and IL-8 all exhibited a statistically significant increase in all the BMS patients versus the healthy volunteers (P < 0.05) but only BDNF was significantly different between patients with anxiety/depression and healthy individuals when considering anxiety/depression. Among BMS patients with anxiety/depression, saliva TNF-α had positive associations with other biomarkers including BDNF, IFN-γ, IL-1β, IL-6, and IL-8 (P < 0.05). The increased concentration of saliva BDNF holds strong potential for diagnosing BMS and the elevated level of saliva TNF-α is crucial in identifying BMS patients with anxiety/depression. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis is a public health problem leading to an increased risk of fractures, negatively impacting women's health. The absence of sensitive and specific biomarkers for early detection of osteoporosis represents a substantial challenge for improving patient management. Herein, we aimed to identify potential candidate proteins associated with low bone mineral density (BMD) in postmenopausal women from the Mexican population. Serum samples from postmenopausal women (40 with normal BMD, 40 with osteopenia (OS), and 20 with osteoporosis (OP)) were analyzed by label-free LC–MS/MS quantitative proteomics. Proteome profiling revealed significant differences between the OS and OP groups compared to individuals with normal BMD. A quantitative comparison of proteins between groups indicated 454 differentially expressed proteins (DEPs). Compared to normal BMD, 14 and 214 DEPs were found in OS and OP groups, respectively, while 226 DEPs were identified between OS and OP groups. The protein–protein interaction and enrichment analysis of DEPs were closely linked to the bone mineral content, skeletal morphology, and immune response activation. Based on their role in bone metabolism, a panel of 12 candidate biomarkers was selected, of which 1 DEP (RYR1) was found upregulated in the OS and OP groups, 8 DEPs (APOA1, SHBG, FETB, MASP1, PTK2B, KNG1, GSN, and B2M) were upregulated in OP and 3 DEPs (APOA2, RYR3, and HBD) were downregulated in OS or OP. The proteomic analysis described here may help discover new and potentially non-invasive biomarkers for the early diagnosis of osteoporosis in postmenopausal women. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH), a common complication in dogs affected by degenerative mitral valve disease (DMVD), is a progressive disorder characterized by increased pulmonary arterial pressure (PAP) and pulmonary vascular remodeling. Phosphorylation of proteins, impacting vascular function and cell proliferation, might play a role in the development and progression of PH. Unlike gene or protein studies, phosphoproteomic focuses on active proteins that function as end-target proteins within signaling cascades. Studying phosphorylated proteins can reveal active contributors to PH development. Early diagnosis of PH is crucial for effective management and improved clinical outcomes. This study aimed to identify potential serum biomarkers for diagnosing PH in dogs affected with DMVD using a phosphoproteomic approach. Serum samples were collected from healthy control dogs (n = 28), dogs with DMVD (n = 24), and dogs with DMVD and PH (n = 29). Phosphoproteins were enriched from the serum samples and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data analysis was performed to identify uniquely expressed phosphoproteins in each group and differentially expressed phosphoproteins among groups. Phosphoproteomic analysis revealed nine uniquely expressed phosphoproteins in the serum of dogs in the DMVD+PH group and 15 differentially upregulated phosphoproteins in the DMVD +PH group compared to the DMVD group. The phosphoproteins previously implicated in PH and associated with pulmonary arterial remodeling, including small nuclear ribonucleoprotein G (SNRPG), alpha-2-macroglobulin (A2M), zinc finger and BTB domain containing 42 (ZBTB42), hemopexin (HPX), serotransferrin (TRF) and complement C3 (C3), were focused on. Their unique expression and differential upregulation in the serum of DMVD dogs with PH suggest their potential as biomarkers for PH diagnosis. In conclusion, this phosphoproteomic study identified uniquely expressed and differentially upregulated phosphoproteins in the serum of DMVD dogs with PH. Further studies are warranted to validate the diagnostic utility of these phosphoproteins. [ABSTRACT FROM AUTHOR]

The circulating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant presents an ongoing challenge for surveillance and detection. It is important to establish an assay for SARS-CoV-2 antibodies in vaccinated individuals. Numerous studies have demonstrated that binding antibodies (such as S-IgG and N-IgG) and neutralizing antibodies (Nabs) can be detected in vaccinated individuals. However, it is still unclear how to evaluate the consistency and correlation between binding antibodies and Nabs induced by inactivated SARS-CoV-2 vaccines. In this study, serum samples from humans, rhesus macaques, and hamsters immunized with inactivated SARS-CoV-2 vaccines were analyzed for S-IgG, N-IgG, and Nabs. The results showed that the titer and seroconversion rate of S-IgG were significantly higher than those of N-IgG. The correlation between S-IgG and Nabs was higher compared to that of N-IgG. Based on this analysis, we further investigated the titer thresholds of S-IgG and N-IgG in predicting the seroconversion of Nabs. According to the threshold, we can quickly determine the positive and negative effects of the SARS-CoV-2 variant neutralizing antibody in individuals. These findings suggest that the S-IgG antibody is a better supplement to and confirmation of SARS-CoV-2 vaccine immunization. [ABSTRACT FROM AUTHOR]

To date, little is known concerning the circulating levels of biochemically relevant metabolites (antioxidants, oxidative/nitrosative stress biomarkers, purines, and pyrimidines) in patients with primary myelofibrosis (PMF), a rare form of myeloproliferative tumor causing a dramatic decrease in erythropoiesis and angiogenesis. In this study, using a targeted metabolomic approach, serum samples of 22 PMF patients and of 22 control healthy donors were analyzed to quantify the circulating concentrations of hypoxanthine, xanthine, uric acid (as representative purines), uracil, β-pseudouridine, uridine (as representative pyrimidines), reduced glutathione (GSH), ascorbic acid (as two of the main water-soluble antioxidants), malondialdehyde, nitrite, nitrate (as oxidative/nitrosative stress biomarkers) and creatinine, using well-established HPLC method for their determination. Results showed that PMF patients have dramatic depletions of both ascorbic acid and GSH (37.3- and 3.81-times lower circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001), accompanied by significant increases in malondialdehyde (MDA) and nitrite + nitrate (4.73- and 1.66-times higher circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001). Additionally, PMF patients have remarkable alterations of circulating purines, pyrimidines, and creatinine, suggesting potential mitochondrial dysfunctions causing energy metabolism imbalance and consequent increases in these cell energy-related compounds. Overall, these results, besides evidencing previously unknown serum metabolic alterations in PMF patients, suggest that the determination of serum levels of the aforementioned compounds may be useful to evaluate PMF patients on hospital admission for adjunctive therapies aimed at recovering their correct antioxidant status, as well as to monitor patients' status and potential pharmacological treatments. [ABSTRACT FROM AUTHOR]

Myelofibrosis (MF) is a hematologic disease characterized by bone marrow fibrosis, cytopenias, splenomegaly, and constitutional symptoms. Recent years have seen the emergence of novel therapeutic agents, notably ruxolitinib and fedratinib, which target the Janus kinases (JAK) pathway. However, their myelosuppressive effect coupled with the persistence, and even worsening anemia remains a significant challenge, leading usually to treatment discontinuation. This review focuses on Momelotinib (MMB), a unique JAK inhibitor that has shown promise in MF treatment, particularly in improving anemia. MMB inhibits type 1 kinase activin A receptor or activin receptor-like kinase-2 (ACVR1/ALK2), with consequent rebalancing of the SMAD pathways and reduced transcription of hepcidin. Moreover, it seems that MMB could reduce the serum levels of several inflammatory cytokines responsible for anemia. Clinical trials have demonstrated MMB's efficacy in reducing spleen size, alleviating symptoms, and improving anemia, with a favorable safety profile compared to other JAK inhibitors, both in treatment-naïve and in pre-treated patients. Due to its mechanism of action, MMB represents a valuable therapeutic option in MF, addressing the clinical challenge of anemia and potentially improving outcomes for patients with hematologic malignancies. Ongoing research explores MMB's potential in acute myeloid leukemia and combination therapies. [ABSTRACT FROM AUTHOR]

The aim of this research was to examine the serum vitamin D status in Gray Shirazi ewes during different reproductive stages, including mating, pregnancy, and early lactation. A total of 60 healthy ewes were sampled at three stages. The first stage was during mating, the second stage was in the late pregnancy, and the third stage was after delivery. The blood samples were analyzed for 25-hydroxy vitamin D levels. At delivery, multiple births, weight of lambs, and stillbirth rates were recorded. The results revealed that the mean serum vitamin D levels were significantly higher in the third stage of sampling (beginning of lactation) compared to the first stage (mating) and the second stage (pregnancy) (P=0.014 and P=0.017). However, there was no significant difference in vitamin D levels among the non-pregnant (the ewes that did not become pregnant after mating), singleton, and twin groups at any of the sampling stages. Vitamin D levels were highest at the beginning of lactation in gray shirazi ewes. Additionally, serum vitamin D was slightly decreased in pregnant ewes as the number of lambing increased. In total, the findings suggest that maintaining sufficient vitamin D levels may play a role in reproductive health in sheep, as there appears to be a correlation between vitamin D levels and fertility. [ABSTRACT FROM AUTHOR]

Acute heat stress contributes greatly to sudden death in animals and induces serious intracorporal damage even if the animal survives. This trial was therefore conducted to unravel the effect of dietary supplementation of acetylsalicylic acid (ASA) on the serum biochemical composition and hormonal status of finisher broiler chickens during the transition from dry to rainy season (January - March). One hundred and ninety-two (192) day-old broiler chicks (ANAK) were randomly allotted to four treatment diets supplemented with 0, 0.025, 0.050, and 0.075% of ASA at 48 birds/treatment in four replicates of 12 birds each. The result revealed that broilers fed 0.075% ASA had the highest (p<0.05) aspartate aminotransferase and alkaline phosphatase with the values of 69.12 ± 6.52 IU/L, 58.02 ± 11.75 IU/L respectively, while broilers fed 0.050% ASA had the lowest (p<0.05) cholesterol value of 57.27 ± 2.61 mg/dL. The highest (p<0.05) total protein value of 4.20 ± 0.11 g/dL was observed in broilers fed the control diet. There were significant treatment effects (p<0.05) in all the hormonal parameters investigated. Estradiol was observed to increase as the level of ASA supplementation increased. Similarly, broilers fed 0.075% ASA had the highest (p<0.05) progesterone value. It could be concluded that ASA supplementation improves serum biochemical profile, as well as reduces the cholesterol level of experimental birds. [ABSTRACT FROM AUTHOR]

The present study aimed to elucidate the short term biodistribution of nano sized graphene oxide (GO) along with the toxicological assessment under in-vivo condition with an intent to analyse the toxic effects of sudden accidental exposure of GO The synthesised GO was characterized using UV-Visible spectroscopy, XRD, FTIR, Raman spectroscopy, TGA and DLS. The morphological imaging was performed using SEM, TEM and AFM. With a lateral size of less than 300 nm, these nanoparticles exhibit significant organ barrier permeability of up to 20%. Upon acute exposure to 10 mg/kg dose of ICG-tagged GO nanoflakes through intravenous route, various organs such as kidney, spleen and liver were observed, and the nanoparticles predominantly accumulated in the liver upon 24 h of exposure. Upon confirming the accumulation of these particles in liver through IVIS imaging, our next attempt was to analyse various biochemical and serum parameters. An elevation in various serum parameters such as ALT, AST, Creatinine and Bilirubin was observed. Similarly, in the case of biochemical parameters tested in liver homogenates, an increase in NO, Catalase, GSH, SOD, ROS, LPO, GR, GPx, and GST was observed. This study highlights the potential toxicological risk associated with GO exposure which must be taken into account for any risk analysis associated with GO based consumer products and the occupational hazards. [ABSTRACT FROM AUTHOR]

Background: Cancer-related anemia (CRA) occurs in a significant proportion of cancer patients and affects disease progression, treatment efficacy, and survival. The chronic inflammatory state associated with cancer is believed to be a major cause of CRA. Tumor necrosis factor alfa (TNF-a) plays a crucial role in the pathogenesis of cancer-related anemia (CRA). Aim: To evaluate TNF-a level, erythropoietin (EPO), and iron status in children with newly diagnosed solid tumors. Methods: This cross-sectional study included 42 children with newly diagnosed solid tumors, recruited from the Pediatric Oncology Clinic at Ain Shams University Children's Hospital by random sampling during the period from June 2022 to February 2023. Twenty-five age- and sexmatched children were enrolled as hospital-based controls. All study participants were subjected to full history taking, through clinical examination and assessment of CBC, iron profile, serum TNF-a and EPO levels. Results: Out of 42 cancer patients, 48%(n=20) were non-anemic (group 1) and, 52%(n=22) were anemic (group 2) with 54.5% (n=12) having functional iron deficiency (FID) anemia. In both patient groups, significantly higher TNFa and lower EPO levels were found compared to controls. Among the anemic group, TNFa negatively correlated with both EPO level and reticulocyte count (p= 0.024) and (p= 0.211) respectively. Conclusion: Patients with CRA have evident state of FID anemia, elevated TNFa and reduced EPO levels. [ABSTRACT FROM AUTHOR]

Aim: To explore the diagnostic value of serum-derived exosomal miRNAs and predict the roles of their target genes in Alzheimer's disease (AD) based on the expression of miRNAs in AD patients. Methods: We determined the relative concentration of exosomal miRNAs by High-throughput Second-generation Sequencing and real-time quantitative real-time PCR. Results: 71 AD patients and 71 ND subjects were collected. The study demonstrated that hsa-miR-125b-1-3p, hsa-miR-193a-5p, hsa-miR-378a-3p, hsa-miR-378i and hsa-miR-451a are differentially expressed in the serum-derived exosomes of AD patients compared with healthy subjects. According to ROC analysis, hsa-miR-125b-1-3p has an AUC of 0.765 in the AD group compared to the healthy group with a sensitivity and specificity of 82.1– 67.7%, respectively. Enrichment analysis of its target genes showed that they were related to neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, the Hippo signaling pathway and nervous system-related pathways. And, hsa-miR-451a had an AUC of 0.728 that differentiated the AD group from the healthy group with a sensitivity and specificity of 67.9% and 72.6%, respectively. Enrichment analysis of its target genes showed a relationship with cytokine-cytokine receptor interactions and the PI3K-Akt signaling pathway. Conclusion: The dysregulation of serum exosomal microRNAs in patients with AD may promote the diagnosis of AD. The target genes of miRNAs may be involved in the occurrence and development of AD through various pathways. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis (CE) is a grievous zoonotic parasitic disease. Currently, the traditional technology of screening CE is laborious and expensive, developing an innovative technology is urgent. In this study, we combined serum fluorescence spectroscopy with machine learning algorithms to develop an innovative screening technique to diagnose CE in sheep. Serum fluorescence spectra of Echinococcus granulosus sensu stricto‐infected group (n = 63) and uninfected E. granulosus s.s. group (n = 60) under excitation at 405 nm were recorded. The linear support vector machine (Linear SVM), Quadratic SVM, medium radial basis function (RBF) SVM, K‐nearest neighbor (KNN), and principal component analysis‐linear discriminant analysis (PCA‐LDA) were used to analyze the spectra data. The results showed that Quadratic SVM had the great classification capacity, its sensitivity, specificity, and accuracy were 85.0%, 93.8%, and 88.9%, respectively. In short, serum fluorescence spectroscopy combined with Quadratic SVM algorithm has great potential in the innovative diagnosis of CE in sheep. [ABSTRACT FROM AUTHOR]

Introduction: Ischemic stroke (IS) is a prevalent disease that poses a significant threat to human life and is responsible for a substantial financial burden. Research has established the crucial role of the miR-17-92 cluster in lung cancer, cardiovascular diseases, and traumatic brain injury. Despite this, few research studies had fully detected the potential of the miR-17-92 cluster as a novel circulating marker for diagnosing IS. Material and methods: miR-17-92 cluster expression in IS was investigated using GSE117064 dataset via bioinformatics analysis. Moreover, qRT-PCR was conducted to further verify miR-17-92 cluster expression in 58 IS individuals and 50 healthy controls (HCs). These cluster members were examined regarding their potential for detecting and diagnosing IS using the ROC method. Results: The expression level of serum miR-20a-5p, miR-19a-3p, miR-18a-5p, and miR-19b-3p was considerably lowered in IS in contrast with HC in both the GSE117064 cohort and clinical cohort. Moreover, these four miRNAs had a fair performance in IS detection. Thereafter, a diagnostic model based on these aforementioned four miRNAs was developed by logistic regression, which had an AUC of 0.974 in the ROC curve. This diagnostic module was verified using the GSE117064 dataset. Further analysis demonstrated an increasing level of the aforementioned miRNAs in day-7 IS patients compared with day-1 IS patients. Conclusions: This research verified the downregulation of the miR-17-92 cluster in IS. This diagnostic model enrolling four cluster members may be a promising biomarker for IS detection. [ABSTRACT FROM AUTHOR]

Dictamnine (DIC), as the most abundant furoquinoline alkaloid ingredient of the herbal medicine Cortex Dictamni (CD), can induce severe liver injury. A previous study found that DIC‐induced liver injury was initiated by cytochrome P4503A (CYP3A)‐mediated metabolic activation and subsequent formation of adducts with cellular proteins. Schisantherin A (SchA) is the major lignan component of the herbal medicine Schisandra chinensis (SC). SC is frequently combined with CD used in numerous Chinese medicinal formulas for the treatment of eczema and urticaria. Furthermore, SC could protect against CD‐induced hepatotoxicity. The objective of the study was to investigate the protective effect of SchA on DIC‐induced hepatotoxicity based on pharmacokinetic interactions. The studies found that SchA exerted a protective effect on DIC‐induced hepatotoxicity in a dose‐dependent manner. Pharmacokinetic studies showed that pretreatment with SchA enhanced the area under concentration‐time curve (AUC) and maximal concentration (Cmax) values of DIC in the serum and liver tissue of mice, indicating that SchA could augment the accumulation of DIC in the circulation. In vitro metabolism assays with mouse liver microsomes (MLMs) showed that SchA reduced the production of DIC–glutathione (GSH) conjugate. In addition, SchA significantly reduced the excretion of DIC–GSH conjugate in the urine of mice and relieved hepatic GSH depletion induced by DIC. These results suggested that SchA could inhibit the metabolic activation of DIC in vitro and in vivo. In summary, our findings showed that the observed pharmacokinetic interactions might be attributable to the inhibition of the metabolism of DIC by SchA, which might be responsible for the protection of SchA against DIC‐induced hepatotoxicity. Therefore, the development of a standardized combination of DIC and SchA may protect patients from DIC‐induced liver injury. SchA exerted the protective effect on DIC‐induced hepatotoxicity in a dose‐dependent manner. Pretreatment with SchA augmented the systemic exposure of DIC in the circulation. SchA inhibited the metabolic activation of DIC in vitro and in vivo. In addition, SchA relieved hepatic GSH depletion caused by DIC. These results implied that the observed pharmacokinetic interactions might be attributable to the inhibition of the metabolism of DIC by SchA, which might be responsible for the protection of SchA against DIC‐induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

The possibility of the differentiation of glioblastoma from traumatic brain injury through blood serum analysis by terahertz time-domain spectroscopy and machine learning was studied using a small animal model. Samples of a culture medium and a U87 human glioblastoma cell suspension in the culture medium were injected into the subcortical brain structures of groups of mice referred to as the culture medium injection groups and glioblastoma groups, accordingly. Blood serum samples were collected in the first, second, and third weeks after the injection, and their terahertz transmission spectra were measured. The injection caused acute inflammation in the brain during the first week, so the culture medium injection group in the first week of the experiment corresponded to a traumatic brain injury state. In the third week of the experiment, acute inflammation practically disappeared in the culture medium injection groups. At the same time, the glioblastoma group subjected to a U87 human glioblastoma cell injection had the largest tumor size. The THz spectra were analyzed using two dimensionality reduction algorithms (principal component analysis and t-distributed Stochastic Neighbor Embedding) and three classification algorithms (Support Vector Machine, Random Forest, and Extreme Gradient Boosting Machine). Constructed prediction data models were verified using 10-fold cross-validation, the receiver operational characteristic curve, and a corresponding area under the curve analysis. The proposed machine learning pipeline allowed for distinguishing the traumatic brain injury group from the glioblastoma group with 95% sensitivity, 100% specificity, and 97% accuracy with the Extreme Gradient Boosting Machine. The most informative features for these groups' differentiation were 0.37, 0.40, 0.55, 0.60, 0.70, and 0.90 THz. Thus, an analysis of mouse blood serum using terahertz time-domain spectroscopy and machine learning makes it possible to differentiate glioblastoma from traumatic brain injury. [ABSTRACT FROM AUTHOR]

The increasing use of molybdate has raised concerns about its potential toxicity in humans. However, the potential toxicity of molybdate under the current level of human exposure remains largely unknown. Endogenous metabolic alterations that are caused in humans by environmental exposure to pollutants are associated with the occurrence and progression of many diseases. This study exposed eight-week-old male C57 mice to sodium molybdate at doses relevant to humans (0.01 and 1 mg/kg/day) for eight weeks. Inductively coupled plasma mass spectrometry (ICP-MS) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS) were utilized to assess changes in urine element levels and serum metabolites in mice, respectively. A total of 838 subjects from the NHANES 2017–2018 population database were also included in our study to verify the associations between molybdenum and cadmium found in mice. Analysis of the metabolome in mice revealed that four metabolites in blood serum exhibited significant changes, including 5-aminolevulinic acid, glycolic acid, l-acetylcarnitine, and 2,3-dihydroxypropyl octanoate. Analysis of the elementome revealed a significant increase in urine levels of cadmium after molybdate exposure in mice. Notably, molybdenum also showed a positive correlation with cadmium in humans from the NHANES database. Further analysis identified a positive correlation between cadmium and 2,3-dihydroxypropyl octanoate in mice. In conclusion, these findings suggest that molybdate exposure disrupted amino acid and lipid metabolism, which may be partially mediated by molybdate-altered cadmium levels. The integration of elementome and metabolome data provides sensitive information on molybdate-induced metabolic disorders and associated toxicities at levels relevant to human exposure. [ABSTRACT FROM AUTHOR]

17β-estradiol (E2), a vital female sex hormone, plays a crucial role in female reproductive cycles and secondary sexual characteristics. The quantification of E2 concentration in human blood and urine samples is essential because a deviation from physiological levels of E2 indicates the development of diseases and abnormalities such as precocious puberty, breast cancer, weight gain, abnormal menstruation, osteoporosis, and infertility. In addition, the detection of E2 in food and the environment has gained widespread interest because of its role as an endocrine disruptor (environmental hormone) that can perturb physiological processes. E2 is used as a drug for hormone therapy. Various E2 detection technologies for diagnosing relevant human diseases, drug screening, and environmental monitoring have been demonstrated in studies. In this article, we have reviewed technological strategies developed for E2 detection with ultrahigh sensitivity, with a limit of detection comparable to several pg/mL or lower. We observed that gold nanoparticles (AuNPs) were used as nanoplatforms for signal amplification, which enabled ultrahigh sensitivity in most studies. Signal amplification was facilitated by AuNP characteristics such as the versatility of surface biochemistry, exceedingly large surface-to-volume ratio, surface plasmonic activity, luminescence quenching ability, and biocompatibility. These techniques have been used to detect E2 in food, water, human serum, and urine with ultrahigh sensitivity. We summarize the working principles of E2 detection strategies that allow ultrahigh sensitivity and provide an approach for future work required for the elucidation of practical applications of these technologies. [ABSTRACT FROM AUTHOR]

The aim of this systematic review is to assess the power of circulating miRNAs as biomarkers as a diagnostic tool in endometriosis. In endometriosis-suspected women with uncertain imaging, the only way to confirm or exclude endometriosis with certainty is currently laparoscopy. This creates a need for non-invasive diagnostics. We searched the literature through the PubMed database using the Mesh terms 'endometriosis' and 'miRNAs'. Some, but limited, overlap was found between the 32 articles included, with a total of 20 miRNAs reported as dysregulated in endometriosis in two or more studies. MiR-17-5p was reported as dysregulated in six studies, followed by miR-451a and let-7b-5p in four studies and miR-20a-5p, miR-143-3p, miR-199a-5p and miR-3613-5p in three studies. Furthermore, a possible impact of the menstrual phase on miRNA expression was noted in five studies, while no influence of hormonal intake was observed in any included study. The modest reproducibility between studies may be attributable to biological variability as well as to the lack of universal protocols, resulting in pre- and analytical variability. Despite the identification of several suitable candidate biomarkers among the miRNAs, the need for high-quality studies with larger and well-defined population cohorts and the use of standardized protocols lingers. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the application value of serum cytokeratin 19 fragment (CYFRA21-1) combined with nerve-specific enolase (NSE), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-Ag) in the diagnosis of lung cancer (LC). Methods: A total of 831 cases of LC, 360 cases of benign lung disease (BLD) and 102 healthy controls, were enrolled. The data were processed using SPSS, GraphPad Prism, and MedCalc software. Results: The tumor marker (TM) levels in the LC and BLD groups were significantly higher than those in the control group; the CYFRA21-1, NSE, and CEA levels in the patients with LC were higher than in those with BLD. In particular, the increase was predominantly observed for the levels of CEA and CYFRA21-1 in adenocarcinoma (LUAD), CYFRA21-1 and SCC-Ag in squamous cell carcinoma (LUSC), and NSE in small cell carcinoma (SCLC). The CYFRA21-1, NSE, and CEA levels were significantly higher in stage IV than in other stages in LC. Univariate binary logistic analysis showed that increased levels of all four TMs were risk factors for BLD and LC. The area under the curve (AUC) of CYFRA21-1 was most effective in distinguishing patients with BLD or LC from the controls and in distinguishing patients with BLD and LC. The AUCs of combined CYFRA21-1, NSE, and CEA were increased to 0.755, 0.922, and 0.783, respectively, with no significant difference with the AUC of the four combined tests. In the histological classification, the best predictors were CEA, for LUAD, CYFRA21-1 for LUSC, and NSE for SCLC. Moreover, the expression levels of CYFRA21-1, NSE, and CEA significantly decreased after each treatment course. Conclusions: The combined assay of CYFRA21-1, NSE, and CEA addresses the aspects of accuracy, sensitivity, specificity, and economic cost and should be considered as a potential diagnostic test in LC. [ABSTRACT FROM AUTHOR]

Varied evidence found for association of serum uric acid with blood pressure in previous studies. The aim of this study is to find out the association of serum uric acid with blood pressure in urban male population of Prayagraj district situated in Uttar Pradesh, India. This was a case-control study conducted in urban settings of Prayagraj district between April to June 2022. The sample size was 200. In this male population of > 35 years and <64 years were taken. Blood pressures, serum uric acid, random blood sugar and serum creatinine were recorded and measured. The American Heart Association (2017) guidelines were used to identify hypertensives. The correlation values are obtained to check the relationship between all three biochemical parameter and blood pressure as well as relative risk is calculated to see the association between them. The receiver operating curve values are obtained to see the predicting potentials of serum uric acid for blood pressure. The mean serum uric acid and random blood sugar for hypertensive cases were found to be quite higher than the mean serum uric acid and mean random blood sugar level of normotensive controls. The correlation was strongest between serum uric acid (0.83, p<0.001) and systolic blood pressure. The area under curve (0.938) values obtained by receiver operator characteristic curve analysis suggests that serum uric acid could be considered as a predictor for hypertension. Hence, serum uric acid was found to be a potential correlate and predictor of hypertension. [ABSTRACT FROM AUTHOR]

The therapeutic effects of saffron have been reported and described in relation to its major derivatives. Among them, in terms of saffron's properties, crocin and crocetin absorption and bioavailability have been the most studied. Nevertheless, the metabolism of these major compounds of saffron has not yet been entirely elucidated. Current data indicate that the phase 2 metabolism of crocetins go through conjugation reactions. Crocetins could also be present in isomeric forms such as other carotenoids. Nonetheless, there are still shadow areas in regard to the measurements of the different circulating forms of crocetins after oral saffron extract administration (Safr'Inside™). In using various approaches, we propose the identification of a new cis isomeric form of crocetin, the 6-cis-crocetin. This compound was found in human serum samples after an oral administration of saffron extract. The 6-cis-crocetin represents 19% of the total crocetin measured after 45 min of consumption. These data mark, for the first time, the presence of a cis isomeric form of crocetin in human serum samples. Moreover, this study led to the development of an analytical method that is able to identify and quantify both isomeric forms (trans and cis). [ABSTRACT FROM AUTHOR]

Purpose. Balance allows multidirectional lower limb movements that improve technical football skills and reduce injury caused by match activities. This study aimed to evaluate the static and dynamic balance of preferred and nonpreferred legs during unipedal stance in young footballers and investigate correlations between the two types of balance across each parameter. Methods. Forty-three youth players (mean age = 15.81 ± 1.33 years, height = 179.50 ± 6.14 cm, body mass = 69.73 ± 9.35 kg) were involved in this study. Static balance was assessed via ellipse area (EA), perimeter length (P), anterior-posterior deviation (APD), medial-lateral deviation (MLD), trunk deviation (TD), average anterior-posterior speed (AAPS), and average medial-lateral speed (AMLS). The total stability index (TSI) and trunk total deviation (TT D) dynamic parameters were also examined. Results. None of the static balance parameters showed significant differences between standing on the preferred and nonpreferred legs. Similarly, no meaningful distinctions were observed between the preferred and nonpreferred legs in terms of dynamic balance parameters. Overall, static and dynamic balances indicated no correlation, although minor connections were found between parameters: TT D and EA (r = 0.332; p = 0.03), TT D and MLD (r = 0.335; p = 0.02), and TT D and TD (r = 0.423; p = 0.01). Conclusions. The balance evaluation in young football players should incorporate dynamic and static assessments because the postural control outcomes in these two tasks are independent. Participants underwent testing for both static and dynamic balance, revealing no noticeable differences between their preferred and nonpreferred legs. [ABSTRACT FROM AUTHOR]

Purpose. This study aimed to assess the impact of four distinct training programs on maximal oxygen uptake (VO2max) and cardiovascular health markers. The programs included: 1) a polarised training program (POL) incorporating sprint interval training (SIT), high-intensity interval training (HIIT) with long intervals, and low-intensity training (LIT); 2) a program focused solely on SIT training; 3) a program focused solely on long interval HIIT training; and 4) a program focused solely on LIT. The outcomes of interest were VO2max, lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) expression, and serum concentration of oxidised low-density lipoprotein (ox-LDL). Methods. This study enrolled 40 physically active individuals, categorised into four groups. Group POL (n = 10) engaged in a comprehensive POL training program, while group SIT (n = 10), group HIIT (n = 10), and group LIT (n = 10) participated in dedicated SIT, HIIT, and LIT training programs, respectively. SIT included 30-second all-out repetitions, HIIT included 3-minute high-intensity repetitions, LIT performed with intensity at the first ventilatory threshold. Throughout five weeks, participants in all groups underwent three weekly training sessions. Preceding and following the experiment, participants underwent an incremental test and a VO2max verification test. Additionally, serum concentrations of lectin-like oxidised lowdensity lipoprotein receptor-1 (LOX-1) and oxidised low-density lipoprotein (ox-LDL) were measured before the incremental test. Results. Following the conclusion of the experiment, notable mixed effects were observed. Specifically, statistically significant increases were identified in VO2max, with a 14.2% enhancement in the POL group and a 9.5% improvement in the HIIT group. Moreover, there were substantial reductions in LOX-1 levels, demonstrating a 51.5% decrease in the POL group and a 61.1% decrease in the HIIT group. Conclusions. The findings led to the conclusion that both the POL and long interval HIIT programs were effective in enhancing VO2max and lowering serum levels of LOX-1 among physically active individuals. [ABSTRACT FROM AUTHOR]