Blood Levels Research Articles

B-type natriuretic peptide informativeness in myocardial revascularization with cardio-pulmonary bypass

The objective was to study the dynamics of B-type natriuretic peptide (BNP) and its relationship with hemodynamic parameters during on-pump coronary artery bypass grafting (CABG), and to evaluate the informativeness of the biomarker as a predictor of myocardial dysfunction.Materials and methods. The study involved 127 patients aged 59 [54–66.75] years with ischemic heart disease who underwent CABG. The BNP blood level was determined in the operating room at stages: I – before surgery (BNP1 ), II – at the end of surgery (BNP2 ). Hemodynamic parameters were analyzed at the same stages. Correlation analysis, logistic regression with the calculation of the odds ratio (OR) and 95% confidence interval (95% CI) and ROC analysis with the calculation of the area under the ROC curve (AUC) were used.Results. BNP1 blood level was 49 [25.6–91.6], BNP2 – 90 [47.8–140.2] pg/ml (p < 0.0001). BNP1 correlated with central venous pressure (CVP) at stage I (rho = 0.212; p = 0.017) and with pulmonary artery wedge pressure (PAWP) at stage II (rho = 0.204; p = 0.045). BNP2 correlated with PAWP at stage II (rho = 0.204; p = 0.045). BNP1 > 52.1 pg/ml was the predictor of ICU length of stay > 24 hours (OR 1.0290, 95% CI 1.0154– 1.0427, p < 0.0001, AUC 0.775), BNP1 > 71 pg/ml was the predictor of inotropic index > 5 c. u. (OR 1.0076, 95% CI 1.0015–1.0138, p = 0.014, AUC 0.705) and BNP1 > 90.8 pg/ml was the predictor of vasoactive inotropic index > 10 c. u. (OR 1.0070, 95% CI 1.0014–1.0126, p = 0.013, AUC 0.727). BNP2 > 67.5 pg/ml was the predictor of ICU length of stay > 24 hours (OR 1.0179, 95% CI 1.0073–1.0287, p < 0.0009, AUC 0.763), BNP2 > 94.3 pg/ml was the predictor of inotropic index > 5 c. u. (OR 1.0063, 95% CI 1.0010–1.0117, p = 0.020, AUC 0.713), BNP2 > 144 pg/ml was the predictor of intra-aortic balloon pumping (OR 1.0037, 95% CI 1 .0000–1.0074, p = 0.048, AUC 0.854), BNP2 > 159 pg/ml was the predictor of vasoactive inotropic index > 10 c. u. (OR 1.0072, 95% CI 1.0006–1.0139, p = 0.033, AUC 0.729) and BNP2 > 161 pg/ml was the predictor of early mortality in the ICU (OR 1.0040, 95% CI 1, 0000-1.0080, p = 0.049, AUC 0.845). Conclusion. In 78.7% of patients undergoing on-pump CABG, BNP blood level does not exceed the upper limit of normal; by the end of surgery, the biomarker level increases by 32.9 [17.7–62.0] pg/ml. Before and at the end of surgery, BNP values are weakly correlated with CVP and PAWP and do not correlate with other hemodynamic parameters. Before surgery, BNP blood level in the range of 52.1–90.8 pg/ml are predictors of ICU stay > 24 hours (AUC 0.775), inotropic scale > 5 (AUC 0.705) and vasoactive-inotropic scale > 10 c. u. (AUC 0.727). At the end of surgery, BNP > 67.5 pg/ml is associated with an ICU stay > 24 hours (AUC 0.763), and BNP > 90.4 pg/ml is associated with inotropic scale > 5 c. u. (AUC 0.713). The BNP, increased to 144.0–161.0 pg/ml, indicates severe myocardial dysfunction, including hemodynamic support with intra-aortic balloon pumping (AUC 0.854), vasoactive-inotropic scale > 10 c. u. (AUC 0.729) and the risk of early mortality in the ICU (AUC 0.845).

Preliminary exploration of the clinical warning value of ischemic modified albumin in the development of pre-eclampsia

Objective: To explore the clinical warning value of ischemic modified albumin (IMA) and IMA to human serum albumin (HSA) ratio (IMAR) in the development of pre-eclampsia (PE) and its severity. Methods: A total of 156 pregnant women with PE admitted to the Haidian District Maternal and Child Health Hospital of Beijing from April 2022 to March 2023 were collected as the PE group, and 156 healthy pregnant women with the same age and gestational age were matched as the control group. PE pregnant women were further divided into severe PE group (78 cases) and non-severe PE group (78 cases). Severe PE pregnant women were divided into emergency group (42 cases) and non-emergency group (36 cases) according to the disease progression time.All pregnant women were stratified according to their HSA levels (<30 g/L, 30-32 g/L, ≥32 g/L), and the peripheral blood IMA, HSA, and IMAR of pregnant women in different periods and subgroups were compared, and also the difference of IMA levels in umbilical artery blood. Bivariate correlation analysis was used to explore the correlation between severe PE and IMA or IMAR, and receiver operating characteristic (ROC) curves was used to analyze the diagnostic value of IMA, HSA, and IMAR for PE and severe PE. Results: (1) The IMA level and IMAR in peripheral serum of pregnant women in the PE group at diagnosis, and the IMA level in umbilical artery blood at delivery, and peripheral serum at 2 days after delivery were higher than those in the control group. The HSA level in peripheral serum was lower than that in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (2) The IMA level and IMAR in the peripheral serum of pregnant women with severe PE were higher than those in the non-severe PE group at diagnosis, while the HSA level were lower than those in the non-severe PE group. The differences were statistically significant (all P<0.05). At diagnosis, the IMA level and IMAR in peripheral serum of pregnant women in the emergency group were higher than those in the non-emergency group, while the HSA level was lower than that in the non-emergency group. The differences were statistically significant (all P<0.05). When diagnosed, the peripheral serum IMA levels of pregnant women in the PE group were compared between subgroups with HSA<30 g/L, 30-32 g/L, ≥32 g/L, and there was no statistically significant difference (F=0.366, P=0.694). However, the IMAR was compared between the three subgroups, and the difference was statistically significant (F=28.544, P<0.001), which increased with the decrease of HSA levels. In the subgroup with HSA≥32 g/L, the peripheral serum IMA level and IMAR of pregnant women in the PE group were higher than those in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (3) The severe PE manifestations positively correlated with peripheral serum IMAR at diagnosis include systolic blood pressure (r=0.279), mean arterial pressure (r=0.212), and urinary protein quantification (r=0.277), while the severe PE manifestations negatively correlated include HSA levels (r=-0.644) and newborn birth weight (r=-0.305), all of which were significantly correlated (P<0.05). (4) The area under curve (AUC) for IMAR diagnosis of PE was 0.875 (95%CI: 0.833-0.916), with the highest diagnostic efficiency at a cutoff value of 2.06, sensitivity of 72.5%, and specificity of 85.1%. The AUC for diagnosing severe PE was 0.871 (95%CI: 0.822-0.919), with the highest diagnostic efficacy at a cutoff value of 2.18, sensitivity of 72.3%, and specificity of 88.3%. The diagnostic efficacy of IMAR for PE and severe PE were higher than those of IMA and HSA levels. Conclusions: The level of IMA and IMAR in pregnant women with PE are higher than those in normal pregnant women. IMA and IMAR are correlated with the severity of PE, with IMAR changes occurring earlier and more significantly. IMAR could be considered as one of the evaluation indicators for the development of PE, or as a more sensitive PE severity warning indicator than HSA.

Bioelectrical Insight: Correlation Cell Count and Electrical Impedance of Whole Blood throughout Storage with an Impedance Analyzer Methode

Blood, a vital tissue comprising blood cells within the plasma matrix, plays a crucial role in transporting oxygen, nutrients, and functional components throughout the body. Insufficient blood levels can lead to disorders or life-threatening conditions, necessitating blood transfusions for those experiencing deficiencies. Blood banks store blood products to meet transfusion needs, emphasizing safety, donor health, patient conditions, cross-matching accuracy, and storage quality. Examining stored blood indicates an individual's physiological response to environmental changes, with quantitative and qualitative changes visible through whole blood cell count and impedance parameters. Electrical impedance spectroscopy, which measures these biological properties, shows that although blood cell count remains stable over 35 days, impedance characteristics change significantly. Analysis of the Nyquist Zriil plot reveals a consistent decrease in Zriil values, indicating reduced extracellular resistance (Res) over time. These impedance changes reflect alterations in blood morphology, providing crucial insights into the quality of stored blood. In conclusion, electrical impedance spectroscopy effectively monitors stored blood quality, detecting significant changes in extracellular resistance over extended storage periods. These findings underscore the importance of regular monitoring and proper management of stored blood to ensure its safety and effectiveness for transfusions.

Mesothelin promotes the migration of endometrioid carcinoma and is associated with the MELF pattern

Mesothelin (MSLN) is expressed in the mesothelium in normal tissues but is overexpressed in various malignant tumors. In this study, we searched for genes that were more frequently expressed in cases of endometrioid carcinoma (EC) with the MELF (microcystic, elongated, and fragmented) pattern using laser microdissection and RNA sequencing, and found that MSLN was predominantly expressed in cases with the MELF pattern. The role of MSLN in EC was analyzed by generating MSLN-knockout and -knockdown EC cell lines. MSLN promoted migration and epithelial–mesenchymal transition (EMT). Moreover, we found that cadherin-6 (CDH6) expression was regulated by MSLN. MSLN is known to bind to cancer antigen 125 (CA125), and we found that CA125 can regulate CDH6 expression via MSLN. Immunohistochemical investigations showed that MSLN, CA125, and CDH6 expression levels were considerably elevated in EC with the MELF pattern. The expression of CA125 was similar to that of MSLN not only in terms of immunohistochemical staining intensity but also the blood level of CA125. Our results showed that MSLN contributes to the migration and EMT of EC cells through upstream CA125 and downstream CDH6. Therefore, MSLN has potential as a therapeutic target for EC with the MELF pattern.

In vivo contribution of Cyp24a1 promoter vitamin D response elements.

CYP24A1 is a multifunctional, P450 mitochondrial 24-hydroxylase enzyme that is responsible for catabolism of the most active vitamin D hormone (calcitriol, 1,25(OH)2D3), its precursor (calcifediol, 25(OH)D3), and numerous other vitamin D metabolites at the 23- and 24-carbon positions. In the kidney, Cyp24a1 is induced by 1,25(OH)2D3, induced by FGF23, and potently suppressed by PTH to tightly control the circulating blood levels of 1,25(OH)2D3. This gene is believed to be under the control of a pair of classic promoter proximal (PRO) vitamin D response elements (VDREs) that are aided by distal, downstream (DS) containing enhancers that we identified more recently. The DS1 enhancer cluster was found to respond to PTH and FGF23 actions in a kidney-specific manner. The DS2 enhancer cluster was found to assist in the response of 1,25(OH)2D3 in kidney, as well as other target tissues. Despite this knowledge, the in vivo contribution of the PRO VDREs to gene expression, what drives Cyp24a1 basal expression in the kidney, how FGF23 activates Cyp24a1, and importantly, how PTH suppresses Cyp24a1, all remain unknown. Here in this study, we utilize homology directed CRISPR to mutate one or both VDREs in the PRO region of the Cyp24a1 gene in vivo in the mouse to address these questions. We found that the VDRE (VDRE1) more proximal to the to the transcriptional start site (TSS) is the dominant VDRE of the pair and mutation of both VDREs leads to a dramatic loss of VDR, a reduction of Cyp24a1 gene expression in the kidney, and a near elimination of 1,25(OH)2D3 induction in the intestine. FGF23 induction of Cyp24a1 was reduced with mutation of the PRO VDREs, however, co-treatment of 1,25(OH)2D3 and FGF23 synergistically increased Cyp24a1 expression even with the loss of the PRO VDREs. PTH suppression of Cyp24a1 gene expression was unchanged with PRO VDRE mutations, despite a minor reduction in total pCREB occupancy. Finally, VDR occupancy was dramatically reduced across the DS enhancers in the Cyp24a1 locus after the PRO VDREs mutation. Taken together, our data suggest a cooperative relationship between the DS and PRO enhancers in the regulation of Cyp24a1 by 1,25(OH)2D3 and FGF23, and despite the overall reduction of CREB on the genome it appeared that suppression either does not rely on CREB or that the PRO VDREs are unconnected to PTH suppression altogether. These studies point to the DS1 region as a basal switch for Cyp24a1 expression and help further define the interconnected genomic control of these hormones on vitamin D catabolism.

A rapid and reliable targeted LC-MS/MS method for quantitative analysis of the Tryptophan-NAD metabolic network disturbances in tissues and blood of sleep deprivation mice

BackgroundTRY-NAD metabolic network includes TRY (tryptophan), 5-HT (5-hydroxytryptamine), KYN (kynurenine), and NAD (nicotinamide adenine dinucleotide) pathway, which plays a significant role in neurological diseases and ageing. It is important to monitor these metabolites for studying the pathological anatomy of disease and treatment of responses evaluation. Although previous studies have reported quantitative methods for several metabolites in the network, the bottlenecks of simultaneously quantifying the whole metabolic network are their similar structures, diverse physico-chemical properties, and instability. Standardized protocols for the whole metabolic network are still missing, which hinders the in-depth study of TRY-NAD metabolic network in laboratory research and clinical screening. ResultsWe developed a LC-MS/MS method for quantifying 28 metabolites in the TRY-NAD network simultaneously. Optimization was done for the mass spectral parameters, chromatographic conditions and sample pretreatment process. The developed method was fully validated in terms of standard curves, sensitivity, carryover, recovery, matrix effect, accuracy, precision, and stability. The pretreatment of 30 samples only takes 90 min, and the LC-MS/MS running time of one sample is only 13 min. With this method, we bring to light the chaos of global TRY-NAD metabolic network in sleep deprivation mice for the first time, including serum, clotted blood cells, hippocampus, cerebral cortex, and liver. NAD pathway levels in brain and blood decreased, whereas the opposite happened in the liver. The 5-HT pathway decreased and the concentration of KYN increased significantly in the brain. The concentration of many metabolites in KYN pathway (NAD+ de novo synthesis pathway) increased in the liver. SignificanceThis method is the first time to determine the metabolites of KYN, 5-HT and NAD pathway at the same time, and it is found that TRY-NAD metabolic network will be disordered after sleep deprivation. This work clarifies the importance of the pH of the extraction solution, the time and temperature control in pretreatment in standardized protocols building, and overcoming the problems of inconsistent sample pretreatment, separation, matrix effect interference and potential metabolite degradation. This method exhibits great prospects in providing more information on metabolic disturbances caused by sleep deprivation as well as neurological diseases and ageing.

Sex-specific associations among neck circumference, the rs9939609 FTO gene polymorphism, and the 14-year risk of metabolic syndrome.

Limited data exist on the relation between neck circumference (NC) and the risk of developing metabolic syndrome (MS). This study investigated sex-specific associations between NC and the 14-year risk of MS and explored the impact of the FTO rs9939609 polymorphism on these associations. This population-based prospective cohort study involved 2,666 participants (1,301 men and 1,365 women), who were free of MS at baseline (2005-2006). Incident MS cases, defined by the presence of 3 or more criteria regarding blood pressure and blood levels of glucose, triglycerides, and high-density lipoprotein cholesterol, were identified through biennial examinations until 2020. NC measurements taken at baseline and between 2013 and 2014 were analyzed using Cox proportional hazard regression to determine sex-specific associations with MS risk. Controlling for potential confounders such as waist circumference (WC), significant associations were observed in both sexes. Individuals in the highest NC quartile exhibited more than a 2-fold higher MS risk than those in the lowest quartile; with hazard ratios of 2.37 (95% CI, 1.74 to 3.22) for men and 2.65 (95% CI, 1.89 to 3.72) for women (p-value for trend <0.001). No significant interaction was found between the FTO polymorphism and NC. In diagnostic test analyses, NC and WC demonstrated comparable area under the curve values in both sexes. The findings suggest that NC is as effective as WC for predicting the incidence of MS.

Genotoxicity of selected cannabinoids in human lymphoblastoid TK6 cells

Natural non-psychoactive cannabinoids such as cannabigerol (CBG), cannabidiol (CBD), cannabichromene (CBC), cannabidivarin (CBDV), and cannabinol (CBN) are increasingly consumed as constituents of dietary products because of the health benefits claims. Cannabinoids may reduce certain types of pain, nausea, and anxiety. Anti-inflammatory and even anti-carcinogenic properties have been discussed. However, there are insufficient data available regarding their potential (geno-)toxic effects. Therefore, we tested CBG, CBD, CBC, CBDV, and CBN for their genotoxic potential and effects on mitosis and cell cycle in human lymphoblastoid TK6 cells. The selected cannabinoids (except CBDV) induced increased micronuclei formation, which was reduced with the addition of a metabolic activation system (S9 mix). CBDV induced micronuclei only after metabolic activation. Mitotic disturbances were observed with all tested cannabinoids, while G1 phase accumulation of cells was observed for CBG, CBD and CBDV. The genotoxic effects occurred at about 1000-fold higher concentrations than are reported as blood levels from human consumption. However, the results clearly indicate a need for further research into the genotoxic effects of cannabinoids. The mechanism of the mitotic disturbance, the shape of the dose–response curves and the possible effects of mixtures of cannabinoids are aspects which need clarification.

Vitamin D3 and cancer risk in healthy subjects: An umbrella review of systematic review and meta-analysis

Vitamin D3, which originates from cholesterol, exerts its influence on immune cells and potentially cancer cells via the metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D3), impacting their proliferation, differentiation, and apoptosis. An umbrella review was conducted to evaluate the potential protective effect of vitamin D3 intake and serum levels on the incidence and mortality of cancer. A systematic search was conducted in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE databases from their inception to October 1, 2023. We included meta-analyses of observational or randomized clinical trials that compared interventions (vitamin D3 intake) or blood levels in a healthy population, with cancer incidence or mortality as outcomes. The grading of evidence certainty followed established criteria, including strong, highly suggestive, suggestive, weak, or not significant. A total of 71 systematic reviews were included. Strong evidence indicated that vitamin D3 supplementation reduced total cancer mortality (odds ratio [OR], 0.9 [95% CI, 0.87-0.92]; P<.01). In the context of site-specific cancers, there exists highly suggestive evidence pointing towards the potential prevention of head and neck, breast, colorectal, lung, and renal cell cancers through the intake of vitamin D3. Furthermore, strong evidence suggests that maintaining sufficient levels of vitamin D3 may effectively lower the risk of renal cell and thyroid cancer (OR=0.76 [95%CI 0.64-0.88]). There is significant evidence that vitamin D3 intake may reduce the incidence of some cancers. Routine assessments to ensure sufficient levels of vitamin D3 and administering supplements to address deficiencies may serve as crucial preventive measures for healthcare systems.

Somatic Structure and Ultrasound Parameters of the Calcaneus Bone in Combat Sports Athletes in Relation to Vitamin D3 Levels.

Background/Objectives: Physical activity is widely recognized for its beneficial effects on bone density during adolescence, which could lead to enhanced bone density in later life, thus acting as a health-promoting activity with long-lasting implications. However, not all studies are conclusive regarding the type, intensity, duration, and frequency of the most effective physical activities. This study focuses on combat sports athletes and examines the relationship between their somatic build and heel bone parameters using ultrasound (USG) and their vitamin D3 levels. Methods: The study included 40 male athletes specializing in various combat sports. The measurements of body height, body mass, skinfold thickness, and bone widths at multiple sites were performed to estimate the somatic build. The USG parameters of the heel bone and the blood levels of vitamin D3 were also recorded. Statistical significance was determined using one-way ANOVA, with differences among sports disciplines also examined. Results: The study found significant differences in the body composition and USG bone parameters among athletes from different combat sports (p ≤ 0.05). The calcaneus stiffness index (SI) and speed of sound (SOS) were significantly higher in athletes with normal vitamin D3 levels compared to those with below-normal levels (p = 0.0015 and p = 0.001, respectively). These findings suggest that vitamin D3 may influence bone stiffness and density. Conclusions: The study underscores the importance of maintaining adequate vitamin D3 levels to support bone mineralization in athletes, particularly those training indoors with limited exposure to sunlight. It also highlights the potential of using USG as a non-invasive method to assess bone health, aiding in the optimization of training programs to prevent injuries and improve performance.

Vitamin A, E, and C levels in maternal blood of patients with idiopathic preterm premature rupture of membranes, spontaneous preterm birth, and term birth

Vitamin A, E, and C levels in maternal blood of patients with idiopathic preterm premature rupture of membranes, spontaneous preterm birth, and term birth

Monitoring of per- and polyfluoroalkyl substances (PFAS) in human blood samples collected in three regions with known PFAS releases in the environment and three control regions in South Germany.

Per- and polyfluoroalkyl substances (PFAS) are known as persistent and bioaccumulative chemicals. The present paper describes the analysis of 969 human blood samples collected in South Germany aiming to determine whether there are statistic significant differences in internal PFAS burden between three regions with known PFAS releases in the environment (study regions) and three regions without known PFAS releases in the environment (control regions). Nine environmental relevant PFAS were analyzed, including the perfluorooctanoic acid (PFOA) substitute 3H-perfluoro-3-[(3-methoxy-propoxy)propanoic acid] ammonium salt (ADONA). We found that concentrations of PFOA and perfluorooctane sulfonate (PFOS) were higher than for all other PFAS in all of the six regions, but all medians of PFOA (between 0.8 and 0.9ng/ml for the study and control regions) and PFOS (between 1.3 and 1.5ng/ml for the study regions and between 1.4 and 1.5ng/ml for the control regions) were below the human biomonitoring values (HBM) I for PFOA (2ng/ml) und for PFOS (5ng/ml) derived by the German HBM Commission. Concentrations of ADONA were below the limit of quantification in all samples. Minor differences were observed in PFAS blood levels between study and control regions. Especially for PFOS and PFOA the medians for women are slightly lower compared to men. In summary, individuals living in regions with known environmental PFAS contaminations show no higher internal PFAS exposure to controls and in comparison to other studies in the literature.

Evaluating the diagnostic potential of gelsolin in gestational diabetes mellitus: A case-control study.

To investigate the association between gestational diabetes mellitus (GDM) and blood levels of gelsolin (an inflammation-related protein thought to be reduced in type 2 diabetes mellitus) and to determine its role in potential diagnosis and neonatal outcomes. This prospective case-control study was conducted at Ankara Etlik City Hospital between November 2023 and February 2024 with 40 pregnant women with GDM and 40 normoglycemic women. Pregnant women aged 18-40 years who were in their 24th to 28th week of pregnancy and had no known chronic disease were included in the present study and it was investigated as to whether there was a significant difference between the two groups in terms of gelsolin levels and neonatal outcome. Gelsolin level was statistically significantly lower in the GDM group than in the control group (P = 0.004). In patients with fasting blood glucose <96 mg/dL, maternal serum gelsolin levels were associated with GDM, with a cut-off of 15.38 or less, showing a sensitivity of 73%, a specificity of 67%, and an area under the curve (AUC) of 0.703 (95% confidence interval [CI] 0.576-0.810, P = 0.002). There was no difference between groups in terms of adverse obstetric outcomes, but gelsolin levels were associated with composite neonatal adverse outcome (macrosomia, Apgar score at 5 min less than 7, preterm birth, need for neonatal intensive care), with a cut-off value of 16.66 or less showing a sensitivity of 84.6%, specificity of 40.7% and AUC of 0.644 (95% CI 0.529-0.748, P = 0.031). Gelsolin could potentially serve as a promising biomarker for the diagnosis of GDM.

The use of capsicum oleoresin microparticles to mitigate hepatic damage and metabolic disorders induced by obesity

Capsicum oleoresin has potential health benefits, particularly against obesity markers. Due to its high pungency, few studies have been done to explore the intake of this ingredient. The objective of this study was to use the Capsicum oleoresin (CO) microencapsulated into a high-fat diet to evaluate its metabolic effect on mice. Two formulation containing 15 % solids were prepared: the first (F1) with 5% CO and 95% emulsifier, and the second (F2) with 2.5% corn oil, 2.5% CO, and 95% emulsifier. These formulation were atomized in a spray dryer. Ultra-Performance Liquid Chromatography determined the capsaicin content for both formulations. Mice were divided into two groups: lean control (normocaloric AIN diet, n = 10) and high fat (HF diet: hypercaloric, n = 30), which were subdivided into three subgroups: HF control diet (n = 10); diet F1: HF + 20 % CO oleoresin microparticles (n = 10); and diet F2: HF + 20 % CO microparticles containing corn oil (n = 10). The animals treated with the microparticles showed lower glucose levels than the HF control. Mice fed with HF-containing CO microparticles had cholesterol blood levels similar to that of the lean group and lower (<100 mg/dL) than that of the HF control group (150 mg/dL). Capsicum oleoresin microparticles added to high-fat diets promoted lower weight gain and protected the liver against hepatic steatosis. Leptin levels for mice fed with HF diet plus CO microparticles averaged between 2 and 5 ng/ml, whereas the fat control group developed leptin resistance. Capsicum microparticles evidenced a protective effect against dyslipidemia compared to the fat control group, which suggests their use as a potential ingredient for the control of obesity.

Enhanced Brain Clearance of Tau and Amyloid-β in Alzheimer's Disease Patients by Transcranial Radiofrequency Wave Treatment: A Central Role of Vascular Endothelial Growth Factor (VEGF).

While drainage/removal of fluid and toxins from the brain by cerebrospinal fluid (CSF) directly into venous blood is well-known, a second drainage route has recently been (re)discovered-meningeal lymphatic vessels (mLVs)-which are responsible for up to half of total brain fluid/toxin drainage. The cytokine vascular endothelial growth factor (VEGF) increases mLV diameter and numbers to increase mLV drainage, resulting in increased mLV drainage. Alzheimer's disease (AD) is characterized by low plasma and CSF levels of VEGF. To determine if non-invasive transcranial radiofrequency wave treatment (TRFT), through modulation of VEGF levels in blood and CSF, can affect removal of toxins tau and amyloid-β (Aβ) from the brain. Eight mild/moderate AD subjects were given twice-daily 1-hour TRFT sessions at home by their caregivers. Blood and CSF samples were taken at baseline and following completion of 2 months of TRFT. In plasma and/or CSF, strong baseline correlations between VEGF levels and AD markers (t-tau, p-tau, Aβ1-40, Aβ1-42) were eliminated by TRFT. This effect was primarily due to TRFT-induced increases in VEGF levels in AD subjects with low or unmeasurable "baseline" VEGF levels. These increased VEGF levels were associated with increased clearance/drainage of tau and Aβ from the brain, likely through VEGF's actions on mLVs. A new mechanism of TRFT is identified (facilitation of brain tau and Aβ clearance via VEGF) that is likely contributory to TRFT's reversal of cognitive impairment in AD subjects. TRFT may be particularly effective for cognitive benefit in AD subjects who have low VEGF levels.

Urinary D-asparagine level is decreased by the presence of glioblastoma

Gliomas, particularly glioblastomas (GBMs), pose significant challenges due to their aggressiveness and poor prognosis. Early detection through biomarkers is critical for improving outcomes. This study aimed to identify novel biomarkers for gliomas, particularly GBMs, using chiral amino acid profiling. We used chiral amino acid analysis to measure amino acid L- and D-isomer levels in resected tissues (tumor and non-tumor), blood, and urine from 33 patients with primary gliomas and 24 healthy volunteers. The levels of D-amino acid oxidase (DAO), a D-amino acid-degrading enzyme, were evaluated to investigate the D-amino acid metabolism in brain tissue. The GBM mouse model was created by transplanting GBM cells into the brain to confirm whether gliomas affect blood and urine chiral amino acid profiles. We also assessed whether D-amino acids produced by GBM cells are involved in cell proliferation. D-asparagine (D-Asn) levels were higher and DAO expression was lower in glioma than in non-glioma tissues. Blood and urinary D-Asn levels were lower in patients with GBM than in healthy volunteers (p < 0.001), increasing after GBM removal (p < 0.05). Urinary D-Asn levels differentiated between healthy volunteers and patients with GBM (area under the curve: 0.93, sensitivity: 0.88, specificity: 0.92). GBM mouse model validated the decrease of urinary D-Asn in GBM. GBM cells used D-Asn for cell proliferation. Gliomas induce alterations in chiral amino acid profiles, affecting blood and urine levels. Urinary D-Asn emerges as a promising diagnostic biomarker for gliomas, reflecting tumor presence and severity.

Disturbances in Biological Parameters in Patients Exposed to Nitrous Oxide Abuse Experience of the Rene Dubos Hospital Centre in Pontoise

Nitrous oxide abuse is increasingly common among young people. It&amp;apos;s a gas consumed at parties, where access is easy and less expensive. It can cause vitamin deficiencies, leading to neurological and non-neurological clinical manifestations. The aim of this study was to establish the blood biology profile of patients hospitalized for neurological disorders in the context of nitrous oxide abuse. Methodology, we conducted a retrospective and prospective descriptive study from January 2021 to April 2023. We studied frequency of consumption, inhaled dose and time of exposure to nitrous oxide. Blood levels of vitamin B12 and B9 were measured. Methylmalonic acid and homocysteine were also measured in the blood. Results include 15 patients recruited during the study period. 7 of the 15 patients used nitrous oxide daily. One patient consumed 9600 grams per week. Ten patients had a delay in toxicity beyond one year. Vitamin B12 blood levels were normal in 8 of 15 patients. On average, vitamin B12 levels were normal at 207.57 pmol/l. Vitamin B9 was not routinely measured in 9 patients. Blood homocysteine levels were elevated in 12 of 13 patients, with a high mean of 83.36 µmol/l. In conclusion, blood homocysteine levels are a more reliable marker than vitamin B12 for demonstrating biological disturbances associated with laughing gas abuse.

The L-lactate dehydrogenases of Pseudomonas aeruginosa are conditionally regulated but both contribute to survival during macrophage infection.

Pseudomonas aeruginosa is an opportunistic pathogen that thrives in environments associated with human activity, including soil and water altered by agriculture or pollution. Because L-lactate is a significant product of plant and animal metabolism, it can serve as a carbon source for P. aeruginosa in the diverse settings that it inhabits. In this study, we evaluate the production and use of two redundant P. aeruginosa L-lactate dehydrogenases, termed LldD and LldA. We confirm that the protein LldR represses lldD and identify a new transcription factor, called LldS, that activates lldA; these distinct regulators and the genomic contexts of lldD and lldA contribute to their differential expression. We demonstrate that the lldD and lldA genes are conditionally controlled in response to lactate isomers as well as to glycolate and ɑ-hydroxybutyrate, which, like lactate, are ɑ-hydroxycarboxylates. We also show that lldA is induced when iron availability is low. Our examination of lldD and lldA expression across depth in biofilms indicates a complex pattern that is consistent with the effects of glycolate production, iron availability, and cross-regulation on enzyme preference. Finally, macrophage infection assays reveal that both lldD and lldA contribute to persistence within host cells, underscoring the potential role of L-lactate as a carbon source during P. aeruginosa-eukaryote interactions. Together, these findings help us understand the metabolism of a key resource that may promote P. aeruginosa's success as a resident of contaminated environments and animal hosts.IMPORTANCEPseudomonas aeruginosa is a major cause of lung infections in people with cystic fibrosis, of hospital-acquired infections, and of wound infections. It consumes L-lactate, which is found at substantial levels in human blood and tissues. In this study, we investigated the spatial regulation of two redundant enzymes, called LldD and LldA, which enable L-lactate metabolism in P. aeruginosa biofilms. We uncovered mechanisms and identified compounds that control the preference of P. aeruginosa for LldD versus LldA. We also showed that both enzymes contribute to its ability to survive within macrophages, a behavior that is thought to augment the chronicity and recalcitrance of infections. Our findings shed light on a key metabolic strategy used by P. aeruginosa and have the potential to inform the development of therapies targeting bacterial metabolism during infection.

Content of ascorbic acid in different skin phototypes in children with vitiligo

Aim. To evaluate the blood level of ascorbic acid in children with vitiligo according to skin phototype.Material and Methods. Blood ascorbic acid levels were analysed in children of different ages (6-15 years) with different types of vitiligo, depending on skin phototype. Patients were divided into two groups according to the degree and localisation of the vitiligo lesions: with non-segmental (n=116) and with segmental (n=134) vitiligo. The area of distribution of the dermatosis and its stage of development were calculated using the VIMAN and VIDA indices, respectively. Serum ascorbic acid levels were determined by liquid chromatography-mass spectrometry. Patients were classified by phototype according to T. Fitzpatrick’s classification.Results and discussion. Among the children with vitiligo studied, skin phototypes II, III and IV were identified, with a predominance of phototype III over the others. Their percentages differed in the two groups studied. In non-segmental vitiligo, there were more children with a light phototype and fewer with a dark phototype compared to the group of children with segmental vitiligo. Ascorbic acid levels were significantly reduced in children with vitiligo compared to a group of healthy children. The most pronounced decrease was observed in the group with non-segmental vitiligo in the 7-9 year age group. In both groups of patients, there was a tendency for ascorbic acid levels to decrease with age.Conclusion. The data obtained indicate that children with vitiligo have lower ascorbic acid levels than healthy children. The tendency to decrease increases with age, especially in patients with a dark phototype. This fact indicates the need to correct vitamin C levels in the body of children with vitiligo.

Development and validation of the UHPLC-MS/MS method for the quantitative determination of 25 PFAS in dried blood spots.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic fluorine-containing compounds largely used in industrial and consumer applications. They tend to bioaccumulate in the human body after intake from various sources in daily life. Following repeated exposure to PFAS, a broad range of adverse health outcomes has been reported. Consequently, monitoring PFAS levels in human blood is of paramount importance for public health policies. In contrast with traditional venipuncture, dried blood spots (DBS) constitute a reliable, cheap, and less invasive technique to allow microsampling by capillary blood collected on a specific device. This work aimed to develop and validate an innovative analytical method, combining quantitative DBS with UHPLC-MS/MS instrumentation to identify and quantify 25 PFAS. The extraction procedure was developed and optimized within the range 2-100ng/mL. Specifically, fortified blood was applied on Capitainer®B devices providing 10 μL of blood volume through a microfluidic channel. After 3h of drying, the extraction was performed by methanol under sonication, followed by centrifugation. Then, the extraction solvent was evaporated; the residue was reconstituted with the mobile phase solution. The validated method evidenced good sensitivity, with limits of detection ranging from 0.4ng/mL (PFODA, PFOS) to 1.0ng/mL (PFOA, 3,6-OPFHpA). The ± 20% acceptability criteria established for intra- and inter-day precision and accuracy were fulfilled for all analytes. High recovery-above 80%-was recorded, whereas significant matrix effect resulted in ion enhancement (> 50%) for 13 analytes. In conclusion, the proposed workflow proved to be reliable, fit for purpose, and easily adaptable in the laboratory routine.