Serum Concentrations Research Articles

Detection of serum composition in pediatric inflammatory multisystem syndrome associated with SARS-CoV-2 and the response for the treatment by FTIR

Pediatric Inflammatory Multisystem Syndrome (PIMS-TS), associated with SARS-CoV-2 infection, is a severe complication after COVID-19 in children. It is caused by the immune reaction to SARS-CoV-2, and usually appears three to six weeks after the infection. Unfortunately, PIMS causes non-specific symptoms, which makes its diagnosis and treatment difficult. In this paper, we propose Fourier Transform InfraRed spectrometry (FTIR) to identify chemical changes in blood serum of children induced by PIMS and caused by subsequent treatment of the syndrome. The results suggest that although the Principal Component Analysis (PCA) of FTIR data did not allow for differentiation of healthy children and children with PIMS before and after the treatment, the implementation of Support Vector Machine (SVM) showed that the accuracy of the FTIR region between 800 cm− 1 and 1800 cm− 1 in PIMS detection is as high as 92% with a sensitivity of 100%. The difference in the chemical compositions of sera from the control group and the children after the treatment was detected in 54%, indicating that the treatment was effective. Indeed, the obtained medical data clearly showed a decrease of C-reactive protein (CRP) and Procalcitonin (PCT) concentration in serum after the treatment. The decision tree showed that peak 1455 cm− 1 could be used as a potential FTIR PIMS marker. Importantly, FTIR data correlates well with medical parameters, however the correlation differs with respect to the groups before and after the treatment.

Short-term manual acupuncture decreased markers of systemic inflammation and altered articular cartilage transcripts in the Dunkin-Hartley model of osteoarthritis.

To investigate indicators of mobility, inflammation, and cartilage remodeling in Dunkin-Hartley guinea pigs (Cavia porcellus) treated with manual acupuncture compared to 2 different comparator acupuncture groups. 12-month-old male Hartleys were randomly assigned to 1 of 3 in vivo experimental groups that received manual acupuncture, needle sheath taps on corresponding acupoints, or off-point acupuncture. Treatments were performed under isoflurane once weekly for 3 weeks, and open-field enclosure monitoring was performed at the same frequency. After final treatments, all animals were euthanized, blood was collected for inflammatory marker analysis, and tissues were collected for histology, immunohistochemistry, and transcript expression analysis. 18 animals were involved: 6 per experimental group. Serum concentrations of complement component 3 and prostaglandin E2 were significantly decreased in the acupuncture group (P < .05). Muscle from acupoint stomach-36 had 6 gene transcripts with altered expressions in the manual acupuncture group compared to comparators. From cartilage/menisci, manual acupuncture resulted in the downregulation of 13 gene transcripts. Nerve growth factor (NGF) immunostaining in all 3 layers of articular cartilage of the medial tibial plateau was greater in the manual acupuncture group relative to the comparator groups. There were no differences in enclosure monitoring parameters or histologic grading. Appreciable changes in voluntary mobility, behavioral or serum biochemical parameters, or stifle histological structure were not seen. Differences in serum inflammatory proteins, the gene expression of cartilage-remodeling transcripts, and NGF protein concentrations in cartilage were elucidated. The short duration of manual acupuncture showed the initiation of beneficial regenerative and remodeling processes.

Dietary supplementation of Astragalus polysaccharide or its nanoparticles enhances testicular hemodynamics, echotexture, scrotal circumference, concentration of testosterone, estradiol, nitric oxide, and total antioxidant capacity, and semen quality in mature Ossimi rams

This study investigated, for the first time, the potential role of Astragalus polysaccharide (APS) and APS nanoparticles on testicular blood flow (TBF) and semen quality in Ossimi rams. Fifteen sexually mature Ossimi rams were allocated randomly into two treated groups that orally administered either nano APS (2 g/ram/day; n = 5) or APS (20 g/ram/day; n = 5) for four weeks and a control group (n = 5). The nano-emulsion was prepared by adding corn oil to the APS solution, sonicated, centrifuged at 20,000 rpm, then washed 3–4 times, and vacuum dried overnight at 40 °C. The antioxidant activity of APS and APS nano-emulsion was evaluated in vitro. Blood collection and ultrasonographic assessment of the testes and supratesticular arteries (STAs) were conducted immediately before treatment (W0) and once weekly for 6 successive weeks after APS and nano APS administration (W1-W6). Serum testosterone (T) and estradiol (E2) concentrations were determined by ELISA kits, while nitric oxide (NO) and total antioxidant capacity (TAC) were measured spectrophotometrically. Moreover, semen collection and evaluation of some sperm parameters were performed once a week. Results revealed decreases (P < 0.05) in the Doppler indices (resistive index; RI, pulsatility index; PI, and systolic/diastolic; S/D) of the testicular arteries at most time points of the study in the nano APS and APS groups. Pixel intensity (PIX) and integrated density (IND) of testicular parenchyma were significantly reduced (P ˂ 0.05) in the treated groups compared to the control one. T, E2, NO, and TAC concentrations increased (P < 0.05) in the treated groups compared to the control one. Increases (P < 0.05) were noticed in the mass motility, progressive motility %, live sperm %, and membrane integrity % in nano APS and APS groups, compared to the control. Rams in the nano APS group had significantly higher (P < 0.05) sperm cell concentration than the control one. In conclusion, this study extrapolated that the dietary administration of APS and its nanoparticles can improve TBF, testicular echotexture, sperm characteristics, and the concentration of serum T, E2, NO, and TAC with a more significant effect in the APS nanoparticles compared with APS. So, it could be recommended as a dietary supplementation (2 g/ram/day) for enhancing the reproductive performance of rams.

Notes from the Field: Serum Concentrations of Perfluoroalkyl and Polyfluoroalkyl Substances Among First Responders to the Maui Wildfires - Hawaii, September 2023.

Notes from the Field: Serum Concentrations of Perfluoroalkyl and Polyfluoroalkyl Substances Among First Responders to the Maui Wildfires - Hawaii, September 2023.

ANTI-MÜLLERIAN HORMONE AS A DIAGNOSTIC MARKER OF POLYCYSTIC OVARY SYNDROME: A SYSTEMATIC REVIEW WITH META-ANALYSIS.

To determine whether serum anti-Müllerian hormone measurement can be used as a diagnostic marker for polycystic ovary syndrome (PCOS) compared to serum androgen measurement and transvaginal/transabdominal ultrasound. A systematic literature review and meta-analysis were conducted. Electronic and manual searches were carried out in the Cochrane Library, Embase, LILACS, PubMed, Scopus, Web of Science, and Google Scholar databases. Studies conducted in humans, published in any language up to August 2023 and addressing the following research question were included: "Can serum anti-Mullerian hormone levels be used as a diagnostic marker of PCOS in comparison to serum androgen levels and transvaginal/transabdominal ultrasound?". Furthermore, only articles that used the Rotterdam (2003) criteria, the National Institutes of Health of 1990 criteria, the Androgen Excess and PCOS Society criteria, or the Evidence-based Guidelines on PCOS from 2013, 2018, and 2023 for diagnosing women with PCOS were included. Two independent reviewers selected the studies, and extracted and analyzed the data. The QUADAS-2 and GRADE tools were used to analyze the risk of bias and certainty of evidence. This systematic review included 45 studies. The studies exhibited a low risk of bias in the "Reference standard" and "Flow and time" domains but showed a moderate risk of bias in the "Patient selection" domain and a high risk of bias in the "Index test" domain. The meta-analysis of the case-control studies demonstrated a sensitivity of 81% and specificity of 82%, whereas the meta-analysis of the cross-sectional studies showed a sensitivity of 80% and specificity of 85%, both with 95% confidence intervals. The certainty of the evidence was rated as "low". This systematic review showed that serum anti-Müllerian hormone levels can serve as a diagnostic marker for PCOS, when factors like age, test standardization, PCOS phenotypes, and body mass index are considered. Otherwise, the anti-Müllerian hormone should be used as an adjuvant to the PCOS diagnostic criteria established through consensus and/or guidelines. Additionally, serum concentrations reflected the severity of this syndrome.

Donut-shaped [NaP5W30O110]14- polyoxometalate as a promising antidiabetic drug-candidate: putative mechanisms of action.

The aim of this study was to elucidate the potential mechanism of the antihyperglycemic action of the donut-shaped Preyssler-Pope-Jeannin polyanion salt (NH4)14[NaP5W30O110] 31H2O (NaP5W30) and its effect on metabolic disorders associated with diabetes. For this purpose, relevant parameters of blood glucose regulation, lipid profile, and electrolyte status were monitored in streptozotocin (STZ)-induced diabetic rats that were orally treated with 20mg/kg/day NaP5W30 for three weeks. The serum insulin concentration was increased in diabetic animals treated with NaP5W30 (20mg/kg/day, per os, three weeks), which could be one of the possible mechanisms of the confirmed antihyperglycemic effect. In addition, the administration of NaP5W30 significantly reduced hyperglycemia and glycated haemoglobin A1c (HbA1c) in STZ-induced diabetic rats, although normoglycemic values were not achieved. Furthermore, a statistically significant 1.3-fold reduction in serum total cholesterol and a 1.7-fold reduction in high-density lipoprotein (HDL) cholesterol were observed in the NaP5W30 treatment group compared to the diabetic control group. In contrast, NaP5W30 had no effect on homeostasis model assessment of insulin resistance (HOMA-IR) index values, electrolyte concentrations, or serum concentrations of low-density lipoprotein (LDL) cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), or total triglycerides. In summary, NaP5W30 effectively improved glycoregulation in diabetic rats via the considerable stimulation of insulin as a putative mechanism. Moreover, NaP5W30 did not affect rat weight or disrupt lipid and electrolyte status, common diabetes-followed side effects and risk factors for various life-threatening complications. Thus, NaP5W30 could be considered a promising antidiabetic drug-candidate that deserves further investigation.

Downregulated PSME3 Contributes to Severe Preeclampsia by Promoting Trophoblast Cell Apoptosis.

Severe preeclampsia (sPE) is a serious condition posing risks to both maternal and fetal health. Based on mass spectrometry analysis, we identified a key protein, PSME3 (proteasome activator subunit 3), an 11S proteasome activator, whose protein level was significantly downregulated in sPE placentas and whose function in sPE remains unknown. PSME3 protein levels in human placental tissue were detected using Western blot, and PSME3 concentration in serum was detected by ELISA assay. The human preeclampsia-like phenotypes of Psme3-/- pregnant mice were examined. Trophoblast cell apoptosis was detected by flow cytometry. Pregnant mice were treated with 9.5% O2 to construct a preeclampsia mouse model for detecting placental Psme3 expression. The regulation of PSME3 expression by hypoxia was detected in trophoblast cell lines treated with 21% O2 or 1% O2. PSME3 protein levels were significantly downregulated in sPE placentas and serum. Pregnant mice with Psme3-/- embryos and placentas spontaneously presented human preeclampsia-like symptoms, including hypertension and proteinuria, increased serum soluble fms-like tyrosine kinase 1 concentration, fetal growth restriction, and increased cellular apoptosis. Mechanically, PSME3 knockdown promoted the apoptosis of trophoblast cells by repressing the degradation of UBE2V2 (ubiquitin conjugating enzyme E2 V2). Moreover, the placentas of hypoxia-induced preeclampsia mice presented significantly reduced Psme3 protein levels and elevated Ube2v2 protein levels. Hypoxia-inducible factor-1α functioned as a transcriptional repressor of PSME3. In sPE placentas, hypoxia of the placenta may lead to the transcriptional inhibition of PSME3. PSME3 deficiency promotes the accumulation of UBE2V2, thereby inducing trophoblast cell apoptosis. Our study provides a new perspective for elucidating the pathogenesis of sPE.

Real-world interpatient variability in the pharmacokinetics of levetiracetam.

Levetiracetam (LEV) is an antiepileptic drug (AED) used to treat a variety of seizures in adult and pediatric populations. It is an ideal AED due to its favorable pharmacokinetic (PK) and pharmacodynamic profile and lack of interactions with other AEDs. This retrospective cohort study was designed to identify covariates that affect LEV clearance and volume of distribution and to generate a population PK model. Adults with a seizure history receiving LEV during hospital admission with a minimum of one serum LEV concentration available were included in the study. Population PK modeling and covariate testing was performed with MONOLIX Suite 2020R1 (Lixoft, France). A total of 162 serum concentrations were collected from 143 patients. Age, sex, body weight descriptors, serum creatinine, creatinine clearance (CrCL), serum albumin, liver enzymes, and total bilirubin were evaluated. Body surface area (BSA) was a significant covariate for the apparent volume of distribution (V/F). The exclusion of BSA as a covariate of V/F increased the objective function value (OFV) 5.6. CrCL was a significant covariate of apparent plasma clearance (CL/F). The exclusion of CrCL increased the OFV by 18.16 and significantly increased the root square error (RSE) % of the between-subject variabilities of the parameters. LEV clearance is an effective predictor of serum concentration. CrCL was a significant covariate influencing LEV clearance, and BSA was found to influence the volume of distribution. Further studies are needed to determine the effect of body weight descriptors on LEV clearance and, ultimately, outcomes.

Metabolic Characteristics of Lame Cows During Puerperium and the Beginning of the Reproductive Period

This study presents findings from two discrete experimental processes that examined the impact of lameness events on two consecutive, critical time points in the annual production cycle of dairy cattle (early in puerperium—first study, and later at the onset of the reproductive period—second study) regarding liver function, glucose levels, milk production, body condition score, and back fat thickness. In the first study, 47 cows (lame group n = 22, control group n = 25) were monitored from 10 days ante partum (ap) to 46 days post-partum (pp). In the second study, 79 cows (lame group n = 52, control group n = 27) were monitored from day 28 ± 5 pp to day 65–72 ± 5 pp. Lame cows had greater gamma-glutamyl transferase (GGT) concentrations in the blood serum compared to control cows (25.83 vs. 23.56, p = 0.02, respectively) early in puerperium, whereas the two groups did not differ in the second study. The concentration of glutamate dehydrogenase (GLDH) was lower for lame compared to control cows in both studies (17.24 vs. 24.60, respectively, p = 0.02 in the first study, and 30.50 vs. 51.10, respectively, p = 0.02 in the second study). The concentrations of aspartate transaminase (AST) and glucose did not differ between groups in both studies. Lame cows had a lower body condition score (BCS) and backfat thickness (BFT) scores compared to the control in both studies overall. The lame cows of the first study experienced a significant loss of milk production, especially during the second month of lactation, while in the second study, milk production remained unaffected. Conclusively, lame cows have lower BCS and BFT values, whereas milk yield can be negatively affected only if lameness occurs early in the puerperium, probably beginning at the dry period. However, the current research shows that acutely lame cows, as described in this study, exhibit only mild alterations in liver function compared to non-lame ones.

Dynamic assessment of blood inflammation markers in patients during the rehabilitation period after surgical treatment for external genital endometriosis

Background. Providing rehabilitation care to women with external genital endometriosis (EGE) after surgical treatment requires an interdisciplinary approach to selecting patient management strategy and biomarkers for objective monitoring of health status.Objective: to determine the feasibility of using inflammatory biomarkers in women undergoing rehabilitation after EGE surgical treatment to assess the quality of care.Material and methods. The study included 40 EGE patients (main group), 40 patients with other gynecological pathologies (comparison group), and 40 nearly healthy women (control group). All participants with gynecological pathologies underwent surgical treatment with subsequent rehabilitation. The severity of the inflammatory process was assessed using the following inflammation biomarkers: serum interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a), citrullinated histone H3 (CitH3), and the neutrophil to lymphocyte ratio (NLR). The dynamics of changes in biomarker levels were measured before surgery, 1 week and 3 months after it.Results. The assessment of inflammatory biomarker serum concentrations indicated the presence of inflammatory processes in patients of both the main and comparison groups. However, the levels of IL-6, TNF-a, CitH3 and NLR among EGE patients were statistically significantly higher compared to similar parameters in women with other gynecological pathologies. One week after surgery, the main group showed a significant increase in concentrations of IL-6, CitH3 and NLR and a decrease in TNF-a levels compared to baseline values. Three months after surgery, a significant reduction in the severity of the inflammatory process in the main group was observed compared to the values obtained 1 week after surgery. In several cases, the levels of inflammatory biomarkers were statistically significantly lower than baseline values. Notably, the serum concentration of CitH3 decreased to levels observed in nearly healthy women.Conclusion. An inflammatory process was recorded in EGE patients, which can be corrected through surgical intervention. Using serum concentrations of CitH3 as a marker for assessing the quality of surgical treatment for EGE and managing patients during the rehabilitation phase was proved to be viable.

Modified Xiao-Qing-Long-decoction prevents inflammation and promotes Nur77 expression in mice with acute respiratory distress syndrome by inhibiting HDAC7 expression

Context Modified Xiao-Qing-Long-decoction (MXQLD) is believed to have the potential to alleviate lung diseases. Objective We explored the effects and mechanisms of MXQLD in acute respiratory distress syndrome (ARDS). Materials and methods Thirty male C57BL/6 mice were randomized into sham (distilled water), model (distilled water), MXQLD (1 g/kg MXQLD), DEX (distilled water + 0.7 mg/kg dexamethasone), MXQLD + oe-HDAC7 (HDAC7 over-expression + 1 g/kg MXQLD) groups. Except for HDAC7 over-expression on day 0 and dexamethasone injection on day 12, all treatments were administered every two days from day 0 to day 10. On day 12, except for the sham group, all mice underwent cecal ligation and puncture surgery to establish ARDS models. After surgery, pulmonary functions, protein concentration of bronchoalveolar lavage fluid (BALF) and lung tissue morphology in mice were detected. Furthermore, pro-inflammatory cytokine concentrations (IL-6, IL-1β, and TNF-α) in BALF supernatant and serum were quantified. Additionally, HDAC7, Nur77, ZO-1, occludin, and claudin protein expressions were detected. Results MXQLD treatment improved pulmonary functions and alleviated lung injury for ARDS mice. Furthermore, MXQLD treatment decreased protein concentration in BALF, and inhibited pro-inflammatory cytokine release in BALF supernatant and serum for ARDS mice. Additionally, MXQLD treatment down-regulated HDAC7 expression, but up-regulated Nur77, ZO-1, occludin, and claudin expressions for ARDS mice. Importantly, the preventive effects of MXQLD in ARDS mice were reversed by HDAC7 over-expression. Discussion and conclusion MXQLD may prevent inflammation and promote Nur77 expression in ARDS by inhibiting HDAC7 expression, indicating that MXQLD may be a promising drug for preventing ARDS.

Different vitamin D supplementation strategies impact serum vitamin D concentrations and the mRNA expression of genes related to vitamin D metabolism, mitochondria respiration, redox balance, and immune system in weanling piglets.

This study compared the effects of different vitamin D supplementation strategies to pre- and post-weaning piglets on vitamin D metabolism and health-related parameters. Sixty Yorkshire-Landrace × Duroc suckling piglets were selected at the first day of age and randomly assigned to one of two vitamin D supplementation strategies (n = 30 pigs per treatment): CTR - oral saline at days 2, 8 and 21 of age and, from weaning (day 21), in-feed supplementation with 2000 IU of vitamin D as cholecalciferol; and VD - oral 25-hydroxycholecalciferol (25(OH)D3) solution at days 2, 8 and 21 of age plus 15-minute exposure to UVB light every second day from day 14 until day 21 and, from weaning, in-feed supplementation with 2000 IU of vitamin D as 25(OH)D3. Piglets were slaughtered (n = 10 pigs per treatment/day) at days 21 (before start in-feed experimental diets), 28 and 35 and blood and tissues samples (jejunum, liver and kidney) were collected. Body weight, concentrations of serum 25(OH)D3 and jejunum, liver, and kidney mRNA expression of genes related to vitamin D, antioxidant system, and immune defense were measured. Body weight was not affected by treatments (P ≥ 0.34). Serum 25(OH)D3 concentrations were greater for VD piglets at day 21, 28 and 35 (P < 0.01). No effect of treatment was detected (P ≥ 0.14) for mRNA expression in the jejunum mucosa. In the liver of VD piglets, mRNA expressions of genes related to the antioxidant system were lower at day 21 (NDUFB2) and at day 28 (BNIP3, GPX4, and MSRA) (P ≤ 0.10). The mRNA analysis in kidney during the overall period detected higher expression of genes related to the mitochondria oxidative phosphorylation (COX17, NDUFB2, and NDUFB6) in VD groups compared to CTR (P ≤ 0.09). The expression of CYP27B1 in kidney was higher at day 28 and CYP24A1 was lower at day 21 but higher at day 35 for VD animals. In conclusion, during the pre-weaning period, dietary 25(OH)D3 supplementation combined with UVB exposure was effective in increasing serum 25(OH)D3 concentrations at weaning whereas in the post-weaning period dietary 25(OH)D3 supplementation at 2000 IU/kg was more efficient then dietary cholecalciferol at similar levels. The overall results indicate that 2000 IU of vitamin D/kg of diet, independently of source, may be enough to improve the vitamin D status of post-weaning piglets. However, the use of dietary 25(OH)D3 may promote a better modulation of vitamin D metabolism and redox balance.

Differential Clinical and Immunological Impacts of Anti-T-Lymphocyte Globulin (ATLG) vs. Anti-Thymocyte Globulin (ATG) in Preventing Graft-Versus-Host Disease Post-Allogeneic Hematopoietic Stem Cell Transplantation: A Comparative Study.

Both anti-T-lymphocyte globulin (ATLG-Grafalon) and anti-thymocyte globulin (ATG-Thymoglobulin) prevent acute and chronic graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite distinct manufacturing and biological characteristics, the two brands of rabbit anti-lymphocyte globulins have never been compared in a prospective way. In this monocentric study, 114 adult patients transplanted with a matched related or unrelated donor after receiving either ATG (n = 50) or ATLG (n = 64) were included to compare their clinical outcomes and broad immune reconstitution parameters. The use of ATLG, compared with ATG, was associated with a 2-fold reduction in Grade II-IV acute GvHD incidence (Cox HR = 0.29; 95% CI 0.14-0.62, p = 0.006), similar relapse incidence, and improved severe GvHD and relapse-free survival (GRFS) (Cox HR = 0.51; 95% CI 0.29-0.91, p = 0.027). Biologically, reduced IL-15 but increased IL-21 serum concentrations and a significant reduction of PD1+ T cells, mainly across all differentiated stages of CD8+ T cells, were observed in the ATLG group. Immunosequencing of vβ T cell receptor (TCR) repertoires showed similar quantitative characteristics in terms of clonality and diversity across the two groups but different qualitative features, with reduced hyper-expanded T cell clones and higher variability in the distribution of complementarity-determining region 3 (CDR3) lengths in the ATLG group. Altogether, these results suggest that ATLG more effectively regulates alloreactive T cell activation, leading to better prevention of acute GvHD while preserving the graft-versus-leukemia response. These findings led us to initiate a multicentric Phase III randomized trial comparing the two anti-lymphocyte globulins. Trial Registration: The biological REAL GREFFE study was registered in clinicaltrial.gov under the number: NCT03357172.

The Lower Concentration of Plasma Acetyl-Carnitine in Epicardial Artery Disease—A Preliminary Report

Coronary artery disease remains an epidemiological challenge as global morbidity is not declining despite the fact that the risk factors are well known. Metabolomic derivatives of atherosclerosis formation have recently gained attention as a possible non-traditional risk factor. The aim of this study was to find potential differences in acetyl-carnitine chain serum concentrations between epicardial artery disease patients and a control group. There were 41 patients (25 men and 16 women), with a median (Q1–Q3) age of 69 (63–73) years, enrolled in the prospective metabolomic analysis. They were divided into two groups based on cine angiography results confirming epicardial artery disease (group 1, n = 25 (61%)) or showing characteristics corresponding to normal angiograms (group 2, n = 16 (39%)). The quantitation of metabolites was performed based on the coronary angiograms. Significant differences related to the plasma concentration of L-Acetyl-carnitine (7.49 (4.79–9.23) µM vs. 9.36 (8.57–10.23) µM (p = 0.009)), Decanoyl-carnitine (0.00 (0.00–0.37) µM vs. 0.36 (0.19–0.44) µM (p = 0.040)), C12:1-carnitine (0.17 (0.14–0.20) µM vs. 0.22 (0.18–0.24) µM (p = 0.008)), trans-2-Dodecenoyl-carnitine (0.10 (0.07–0.13) µM vs. 0.13 (0.10–0.15) µM (p = 0.002)), cis-5-Tetradecenoyl-carnitine (0.03 (0.02–0.04) µM vs. 0.04 (0.03–0.05) µM (p = 0.043)), and 3,5-Tetradecadien-carnitine (0.16 (0.14–0.18) µM vs. 0.18 (0.17–0.27) µM (p = 0.007)) in group 1 vs. group 2 were noted. Increased plasma levels of acetyl-carnitine may be characteristic of patients with normal coronary angiograms.

Analysis of serum natalizumab concentrations obtained during routine clinical care in patients with multiple sclerosis: A cross-sectional study.

Natalizumab is a humanized monoclonal antibody administered at a fixed dose of 300 mg intravenously or subcutaneously every 4-6 weeks to treat relapsing-remitting multiple sclerosis. In this prospective cross-sectional study, natalizumab serum concentrations obtained during routine healthcare were measured, and the relationships between different routes of administration, sampling times, body characteristics, changes in blood count, and presence of anti-natalizumab antibodies were evaluated. Ninety-two patients were included in this study. Blood samples were collected 0-48 days after administration, and natalizumab serum and anti-natalizumab antibody concentrations, as well as blood counts were measured. Subsequently, patients were divided into three groups according to the collection time after natalizumab administration. During the entire monitored period, serum natalizumab concentrations ranged from 1.8 to 193.3 µg/mL and 1.8 to 100.3 µg/mL after intravenous and subcutaneous administrations, respectively. A significant inverse correlation was found between serum natalizumab concentrations and differential and absolute peripheral blood neutrophil counts, erythrocyte counts, and hemoglobin concentrations. Although all patients were treated with the same dose, a 30-fold difference in serum natalizumab concentrations was observed. This wide inter-individual variability can potentially lead to an increased risk of natalizumab adverse events or, conversely, suboptimal therapeutic concentrations with the risk of further worsening of multiple sclerosis.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) from contaminated water and risk of childhood cancer in California, 2000-2015.

Few studies have investigated associations between per- and polyfluoroalkyl substances (PFAS) and childhood cancers. Detectable levels of PFAS in California water districts were reported in the Third Unregulated Contaminant Monitoring Rule for 2013-2015. Geocoded residences at birth were linked to corresponding water district boundaries for 10,220 California-born children (aged 0-15 years) diagnosed with cancers (2000-2015) and 29,974 healthy controls. A pharmacokinetic model was used to predict average steady-state maternal serum concentrations of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) from contaminated drinking water. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) per doubling of background exposure were calculated for cancers with at least 90 cases. Predicted PFOS and PFOA maternal serum concentrations ranged from background (5 ng/ml PFOS and 2 ng/ml PFOA) to 22.89 ng/ml and 6.66 ng/ml, respectively. There were suggestive associations between PFOS and nonastrocytoma gliomas (n = 268; AOR = 1.26; 95% CI: 0.99, 1.60), acute myeloid leukemia (n = 500; AOR = 1.14; 95% CI: 0.94, 1.39), Wilms tumors (n = 556, AOR = 1.15; 95% CI: 0.96, 1.38), and noncentral system embryonal tumors (n = 2,880; AOR = 1.07; 95% CI: 0.98, 1.17), and between PFOA and non-Hodgkin lymphoma (n = 384; AOR = 1.19; 95% CI: 0.95, 1.49). Among children of Mexico-born mothers, there was increased risk of Wilms tumor (n = 101; AORPFOS = 1.52; 95% CI: 1.06, 2.18; AORPFOA = 1.59, 95% CI: 1.12, 2.24) and noncentral system embryonal tumors (n = 557; AORPFOS = 1.24, 95% CI: 1.03, 1.50; AORPFOA = 1.19, 95% CI: 0.98, 1.45). Results suggest associations between predicted prenatal maternal PFAS serum concentrations and some childhood cancers. Future analyses are warranted.

Persistent organic pollutants and endogenous sex-related hormones in Hispanic/Latino adults: The Hispanic Community health study/study of Latinos (HCHS/SOL).

Previous studies have demonstrated associations of persistent organic pollutants (POPs) with sex-related hormones; however, findings were inconsistent. Sex-specific impacts and pathways through which adiposity influences associations are not completely understood. We sought to evaluate sex-specific associations of POPs serum concentration with sex-related hormones and to explore pathways through which adiposity may modify associations. We studied 1073 men and 716 postmenopausal women participating in the "Persistent Organic Pollutants, Endogenous Hormones, and Diabetes in Latinos" ancillary study which is a subcohort of the "Hispanic Community Health Study/Study of Latinos." We use baseline examination data collected from 2008 to 2011 to investigate associations between eight organochlorine pesticides (OCPs), five polychlorinated biphenyls (PCB) groups, sum of polybrominated diphenyl ethers and polybrominated biphenyl 153 on sex hormone binding globulin (SHBG) and various sex-related hormone levels. We examined associations cross-sectionally using linear and logistic regression models adjusted for complex survey design and confounders. PCBs and select OCPs were associated with increased SHBG in women and decreased estradiol (E2) and/or bioavailable E2 in men. For instance, per quartile increase in serum concentrations of ∑PCBs and oxychlordane were associated with decreased levels of E2 (β=-6.36pmol/L; 95% CI: 10.7,-2.02 and β=-5.08pmol/L; 95% CI: 8.11,-2.05) and bioavailable E2 (β=-4.48pmol/L; 95% CI: 7.22,-1.73 and β=-4.23pmol/L; 95% CI: 6.17,-2.28), respectively, in men, and increased levels of SHBG (β=7.25nmol/L; 95% CI:2.02,12.8 and β=9.42nmol/L; 95% CI:4.08,15.0), respectively, in women. p,p'-DDT and β-HCCH, and o,p'-DDT were also associated with decreased testosterone (T) and bioavailable T (ng/dL) levels in men. Adiposity modified associations in men, revealing stronger inverse associations of PCBs, PBDEs, and several OCPs with LH, SHBG, E2, bioavailable E2, T, and the ratios of LH to FSH and E2 to T in those with below median body mass index and waist-to-hip ratio. Distinct patterns of hormone dysregulation with increasing POPs serum concentration were identified in men and post-menopausal women. In men but less so in postmenopausal women, adiposity modified associations of POPs serum concentration with sex-related hormones.

Chronic cadmium exposure to minimal-risk doses causes dysfunction of epididymal adipose tissue and metabolic disorders.

Cadmium (Cd) is among the top seven most hazardous environmental contaminants. Minimal risk levels for daily exposure have been established, such as no observable adverse effect level (NOAEL) and lowest observable adverse effect level (LOAEL). Chronic exposure to Cd, at both NOAEL and LOAEL doses, causes toxicity in diverse tissues. However, Cd toxicity in adipose tissue, an endocrine and metabolic organ, remains relatively understudied. We aimed to investigate the potentially toxic effects of chronic Cd exposure (at NOAEL and LOAEL doses) on epidydimal adipose tissue of adult male Wistar rats. Ninety male Wistar rats were divided into three groups (n=30): Control Cd-free, NOAEL, and LOAEL that received CdCl2 in drinking water for 15days to 5months. We evaluated over time zoometry, serum and adipose Cd concentration, redox balance, GLUT4 and Nrf2 expression, histology, leptin, adiponectin, adipose insulin resistance index, free fatty acids, and glucose tolerance. The higher dose group showed a more pronounced and sustained increase in serum and adipose tissue of Cd concentration. Zoometry was similarly affected in both Cd-exposed groups with adipocyte hypertrophy. The redox balance was maintained due to the augmenting of Nrf2 expression. Leptin concentration augmented, while adiponectin diminished. Adipose insulin resistance increased simultaneously to lipolysis and glucose intolerance despite high GLUT4 expression. In conclusion, this study provides strong evidence that chronic Cd exposure, even at minimal risk levels (LOAEL and NOAEL doses), has toxic effects, disrupting the function of epididymal adipose tissue and contributing to metabolic disorders.

Iron Chelation Prevents Age-Related Skeletal Muscle Sarcopenia in Klotho Gene Mutant Mice, a Genetic Model of Aging.

A decline in skeletal muscle mass and function known as skeletal muscle sarcopenia is an inevitable consequence of aging. Sarcopenia is a major cause of decreased muscle strength, physical frailty and increased muscle fatigability, contributing significantly to an increased risk of physical disability and functional dependence among the elderly. There remains a significant need for a novel therapy that can improve sarcopenia and related problems in aging. Iron accumulation, especially catalytic iron (labile iron) through increased oxidative stress, could be one of the contributing factors to sarcopenia. Our study aimed to examine the effect of an iron chelator on age-related sarcopenia in mice. We investigated the effect of iron chelation (deferiprone, DFP) in sarcopenia, using mice with klotho deficiency (kl/kl), an established mouse model for aging. Four weeks old Klotho -/- male mice were treated with 25 mg/kg body weight of iron chelator deferiprone in drinking water for 8-14 weeks (n = 12/group, treated and untreated). At the end of the study, gastrocnemius, quadriceps and bicep muscles were dissected and used for western blot and immunohistochemistry analysis, histopathology and iron staining. Serum total iron, catalytic iron and cytokine ELISAs were performed with established methods. Treatment with DFP significantly reduced loss of muscle mass in gastrocnemius and quadriceps muscles (p < 0.0001). Total and catalytic iron content of serum and iron in muscles were significantly (both p < 0.0001) lower in the treated animals. The inhibitory factor of myogenesis, the myostatin protein in gastrocnemius muscles (p = 0.019) and serum (p = 0.003) were downregulated after 8 weeks of therapy accompanied by an increased in muscle contractile protein myosin heavy chain (~2.9 folds, p = 0.0004). Treatment decreased inflammation (serum IL6 and TNFα) (p < 0.0001, p = 0.005), respectively, and elevated insulin-like growth factor levels (p = 0.472). This was associated with reduced DNA damage and reduced 8-hydroxy 2 deoxyguanosine in muscle and HO-1 protein (p < 0.001, p = 079), respectively. Significant weight loss (p < 0.001) and decreased water intake (p = 0.012) were observed in untreated mice compared to treatment group. Kaplan-Meier survival curves show the median life span of treated mice was 108 days as compared to 63 days for untreated mice (p = 0.0002). In summary, our research findings indicate that deferiprone reduced age-related sarcopenia in the muscles of Klotho-/- mice. Our finding suggests chelation of excess iron could be an effective therapy to counter sarcopenia. However, additional studies are needed to evaluate and determine the efficacy in humans.

Ningxiang pig-derived Lactobacillus reuteri improves the gut health of weaned piglets by regulating intestinal barrier function and cytokine profiles

Weaning stress in piglets can induce intestinal damage, resulting in impaired growth performance. Probiotics have emerged as significant contributors to enhancing gut health in piglets. This study aimed to evaluate the effects of Lactobacillus reuteri (L. reuteri) supplementation on growth performance, intestinal immunity, and intestinal barrier integrity in weaned piglets. In this investigation, fourteen healthy weaned piglets of similar age and weight, were randomly assigned to two groups (n = 7), receiving either normal saline (Control group) or L. reuteri (L-treatment group) over a 16-day period. The findings revealed no significant impact of L. reuteri on growth performance compared to controls. However, it lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P < 0.05) and elevated serum concentrations of Immunoglobulin A (IgA), immunoglobulin G (IgG), and secretory immunoglobulin A (sIgA) (P < 0.05). Additionally, L. reuteri notably enhanced the villus height-to-crypt depth ratio in the ileum (P < 0.05) and increased mRNA expression of zonula occludens-1 (ZO-1), Claudin-1, and ZO-1 in ileal tissue (P < 0.05). Furthermore, L. reuteri reduced mRNA expression of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) (P < 0.05) in the jejunum and colon while enhancing the expression of the anti-inflammatory cytokine interleukin-10 (IL-10) (P < 0.05) in both the ileum and colon. This study demonstrates that L. reuteri isolated from Ningxiang pigs can improve the intestinal health of weaned piglets by modulating gut barrier function and cytokine levels.