Significant Increase In Serum Concentration Research Articles

Supplementation with mulberry leaves improves growth performance and meat quality of Xiangdong black goats.

Mulberry (Morus alba) leaf (ML) is a high-quality feed source for ruminants, while it is unclear whether it can enhance the growth performance and meat quality of Xiangdong black goats. In this study, we investigated the effects of ML supplementation (0, 5, 10, 15, and 20%) on the growth performance, serum variables, and the profiles of amino acids and fatty acids in the muscle of Xiangdong black goats. Results showed that the final body weight, initial and final dry matter intake, and average daily gain increased linearly and quadratically with the increasing ML content (P < 0.05). The serum concentrations of total antioxidant capacity (T-AOC) increased linearly, while immunoglobulin G (IgG) increased quadratically with the increasing ML content (P < 0.05). Conversely, the saturated fatty acids (SFA) content in meat decreased linearly with the increasing ML content (P < 0.05). Compared to goats without ML supplementation, goats fed with 15% ML showed significant increases in serum concentrations of T-AOC, superoxide dismutase, catalase, and IgG (P < 0.05). Furthermore, goats fed with 20% ML displayed significant decreases in SFA (C18:0) content, compared to goats without ML supplementation (P < 0.05). These results suggest that ML supplementation promotes the growth performance of goats. A diet containing 15% ML showed better effects in promoting antioxidant and immunomodulatory activities, while a diet with 20% ML was more effective in enhancing meat flavor in Xiangdong black goats.

The effect of systemic acetazolamide administration on intraocular pressure in healthy horses-A preliminary study.

In equine glaucoma, topical treatment with carbonic anhydrase inhibitors (CAIs) is recommended. Oral acetazolamide, a systemic CAI, is used in horses with hyperkalemic periodic paralysis. Information regarding its effect on equine intraocular pressure (IOP) is scarce. The aim of the study was to determine the effect of oral acetazolamide treatment on IOP in horses, in a case-control study. Ten healthy horses. Horses were treated with oral acetazolamide (4.4 mg/kg) BID for 1 week. Serum acetazolamide concentrations were determined by liquid chromatography/tandem mass spectrometry, and IOP were measured before treatment, daily during treatment, and at 48 and 72 h after treatment. Acetazolamide serum levels reached steady state at 72 h after the first oral dose. In a mixed effect model logistic regression, there was a significant decrease in IOP on the third treatment day, of 2.4 mmHg (p = .012) and 2.7 mmHg (p = .006) in the left (OS) and right eye (OD), respectively. On the seventh day, there was a decrease in 2.5 mmHg (p = .008) and 2.7 mmHg (p = .007) OS and OD, respectively. A significant increase occurred 48 h following treatment discontinuation (3.6 mmHg, p < .001 and 3.5 mmHg, p < .001 OS and OD, respectively). The area under the concentration versus time curve (AUC(0-10h)) was 1.1 ± 0.5 μg/mL*h, mean residence time 6.7 ± 4.3 h, peak plasma concentration (Cmax) 0.4 ± 0.4 μg/mL and time to reach Cmax 1.8 h. There was a significant increase in serum concentrations 1, 2, 48, 72, and 156 h following the first drug administration (p < .05). Further studies are required to determine whether acetazolamide is a potential treatment for equine glaucoma.

Relationship between Serum Concentrations and Muscular Expressions of Selenoproteins on Selenium-Supplemented Insulin Resistance Mouse Model.

Previously, insulin resistance and hepatic oxidative stress with increased expressions of glutathione peroxidase (GPx) 1 and selenoprotein P (SelP) were induced in NSY mice, a diabetic mouse model, by administrating a high fat diet (HFD) and seleno-L-methionine (SeMet) for 12 weeks. In this study we developed an analysis method for serum selenoproteins using LC-tandem mass spectrometry (LC-MS/MS) and investigated the effects of supplementary selenium on serum concentrations of selenoproteins as well as protein expression in skeletal muscle as a major insulin target tissue under the same experimental condition. The glucose area under the curves for oral glucose tolerance and insulin tolerance tests indicated that the HFD induced insulin resistance, whereas the treatment of SeMet + HFD showed insignificant promotion compared with the HFD-induced insulin resistance. Although the expressions of GPx1 in gastrocnemius and soleus were not significantly induced by supplementary SeMet nor HFD administration, the expressions of SelP in both skeletal muscles were significantly induced by the treatment of SeMet + HFD. There were also significant increases in serum concentrations of SelP by supplementary SeMet + HFD administration, whereas GPx3 was augmented by supplementary SeMet only. These results indicated that the HFD intake under the sufficient selenium status augmented the blood secretion of SelP, which may participate in the reduction of insulin sensitivity in skeletal muscles as well as liver or adipose tissues, and it is a better indicator of deterioration than GPx3 as it is a major selenoprotein in serum.

Effect of Soybean, Groundnut, Crayfish Inclusion and Vitamin C-fortified Formulated Food Blends on Biochemical, Hematological, Protein Quality and Performance Indices in Weanling Albino Rats

In this study, food staples comprising of Zea mays (maize), Sorghum bicolor (guinea corn), Glycine max (soybean), Arachis hypogea (groundnut) and Procambarus clarkii (crayfish) were traditionally processed and formulated into maize-guinea corn based weaning diets at 16% protein level. A replica of each diet was formulated with inclusion of vitamin C (50 mg/100 g diet). Fifty four 3-week old weanling albino rats (Rattus norvegicus) weighing between 36-39 g were placed into 13 groups of 4 rats per group and administered different diet groups ranging from maize- guinea corn base diet alone, through staples-inclusive diet (singly and in combination) and their vitamin c fortified replica diets, and standard commercial infant formula (Cerelac®) diet. Animals were sacrificed on the 28th day from onset of feeding and evaluated for biochemical, hematological and biological parameters; and sensory evaluation also conducted on the diets. Results showed significant increases in serum concentrations of protein, urea, creatinine; in the levels of red blood cell (RBC), hemoglobin (Hb) and packed cell volume (PCV); in total body weight gain and organ weights and insignificant changes in white blood cell (WBC) and platelet counts in the staples-inclusive diets compared to base diet and also in the vitamin C- fortified diets compared to non-fortified diets. Incorporation of food staples enhanced the protein quality of the diets while fortification with vitamin C increased only the biological value. On the acceptability rating, only the base gruel-crayfish mix showed significantly higher taste and overall acceptability. Therefore, the inclusion of the food blends comprising of soybean, groundnut and crayfish improved the nutritive content, hematopoietic potential, protein quality, taste and overall acceptability of the maize-guinea corn based weaning diet. These were further improved by fortification of the diets with vitamin C, while crayfish played a prominent role in taste and overall acceptance of the formulated diets. Fortification also significantly bridges the gap between the formulated weaning diets and Cerelac®, a standard commercial weaning formula in Nigeria.

Vitamin D Supplementation: Effect on Cytokine Profile in Multiple Sclerosis

Vitamin D is known for its role in modulating calcium and phosphate homeostasis and is implicated both in bone mineralization and immune system regulation. The immune-modulatory role of vitamin D and its impact on multiple sclerosis (MS) courses are still debated. The aim of this review was to check the effect of vitamin D supplementation on cytokine profile regulation in people with MS. A significant increase in serum concentrations of interleukin (IL)-10 and Transforming growth factor (TGF)-β1 after vitamin D supplementation was demonstrated in most studies, with some of them reporting a reduction in disability scores after vitamin D supplementation and an inverse correlation between IL-10 levels and disability. The effect of vitamin D on the serum levels of IL-17 and IL-6 was controversial; different results across studies could be explained by a variability in the treatment duration, route, and frequency of administration, as well as the dosage of vitamin D supplementation, responses to vitamin D treatment and the serum levels reached with supplementation, including the methods used for cytokine analysis and the different cell types investigated, the MS phenotype, the disease phase (active vs. non-active) and duration, and concomitant treatment with disease-modifying therapies. Nevertheless, the significant increase in the serum concentrations of IL-10 and TGF-β1, demonstrated in most studies, suggests an anti-inflammatory effect of vitamin D supplementation.

Evaluation of Aspergillus meal prebiotic in productive parameters, bone mineralization and intestinal integrity in broiler chickens

This study investigates the effects of Aspergillus meal prebiotic on a spectrum of parameters, including productive performance, bone mineralization, and intestinal integrity, in broiler chickens. Day-of-hatch Cobb 500 by-product male chicks (320 total) were randomly assigned to two experimental groups (G1 and G2) in floor pens (150×300 cm), each pen containing separate feeders and watering systems (8 replicates per treatment, 20 birds/pen). Chickens kept in G1 (control) were fed a basal diet, while those of G2 (treated) were fed a basal diet supplemented with 0.2% PRI-A-FERM. Performance parameters, including body weight (BW), body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR), were evaluated weekly from the 7th day to the end of the trial at 42 d. Fluorescein isothiocyanate-dextran (FITC-d) was administered via oral gavage to 3 chickens/replicate (n = 24), and blood was collected on 21d and on 42d to determine serum concentration of FITC-d as a biomarker to evaluate intestinal permeability and peptide YY as an indirect biomarker to evaluate short chain fatty acids. Chickens that received the \textit{Aspergillus} meal prebiotic showed a significant increase in BW, BWG, and FI on days 14, 21, 28, 35, and 42 (P&lt;0.05) and a significant reduction in FCR on days 28, 35, and 42 of evaluation compared to control. Moreover, chickens that were supplemented with the Aspergillus meal prebiotic showed a significant reduction in serum concentrations of FITC-d on both days of evaluation, as well as a significant increase in serum concentration of peptide YY. Additionally, treated animals significantly increased bone strength, total bone ash, and calcium and phosphorous content at both evaluation times compared to the control. In summary, the results of this study suggest that Aspergillus meal prebiotic supplementation can positively influence productive parameters, bone mineralization, and intestinal integrity in broiler chickens. The observed improvements underscore the importance of gut health in overall poultry performance. The findings contribute to the growing body of knowledge on the benefits of prebiotics (0.2%, PRI-A-FERM) in animal nutrition and highlight the potential for their practical application in enhancing poultry production systems. Further research is warranted to elucidate the underlying mechanisms and optimize prebiotic utilization for improved broiler health and productivity

Ceruloplasmin and some biochemical parameters as a marker for acute myeloid leukemic patients

Acute myeloid leukemia is a second type of leukemia and has more effect on elder patients than adult. This research's objective was to measure the serum levels of ceruloplasmin (CP), ferritin (FR), vitamin B12 (VitB12), folic acid (FA), zinc (Zn), copper (Cu), and iron (Fe) in acute myeloid leukemic patients (AML) (before and after taking chemotherapy) and healthy control groups. In this study, about (160) blood samples (males and females) were collected from acute myeloid leukemic patients in Erbil’s Nanakali hospital and they were separated into four groups: Group 1 (G1) including (40) Apparently healthy control group, Group 2 (G2) include (40) acute myeloid leukemic patients before taking chemotherapy (new cases), Group 3 (G3) include (40) acute myeloid leukemia patients taking chemotherapy for one cycle, and Group 4 (G4) include (40) acute myeloid leukemic patients with taking chemotherapy for more than one cycle. The outcomes display a significant increase in serum concentration of ceruloplasmin, ferritin, vitamin B12, and iron in all patient groups when compared with control groups. While the serum concentration of folic acid, zinc, and copper decreased in all patient groups when compared with the healthy control group. In addition, the correlation analysis displays that there was a significant positive correlation between ceruloplasmin with ferritin, vitamin B12, and iron, on another hand have a non-significant negative correlation between ceruloplasmin with folic acid, zinc, and copper. According to the present study, there was a direct correlation between AML patients with the serum levels of CP, FR, VitB12, FA, Zn, Cu, and Fe. A high area under the curve of our data suggests that testing for (CP, FR, VitB12, FA, Cu, and Fe) could be helpful to detect AML. However, zinc is not a good biomarker for detecting AML patients.

Issues of cytokine regulation in vibration disease and associated conditions

The article presents the data on the state of cytokine regulation and indicators of endothelial damage when exposed to industrial vibration (general or local) and in combination with arterial hypertension. Changes in the levels of pro-inflammatory and anti-inflammatory cytokines are described, and biomarkers of endothelial dysfunction in the combined course of vibration disease and arterial hypertension are investigated. The study of the cytokine profile and biomarkers of damage to the vascular endothelium in this pathology will allow making early diagnosis of vascular disorders and optimizing preventive measures for workers in vibration hazard industries. Purpose of the study. Improving the quality of early diagnosis and prevention of vibration dis ease in an isolated course and its combination with arterial hypertension based on a study of the cytokine profile and biomarkers of endothelial dysfunction in this pathology. Material and research methods. A comprehensive study included 84 patients with vibration disease from the exposure to local and general vibration of the first and second degree, 61 patients with a combined course of vibration disease from the exposure to local and general second degree vibration and arterial hypertension, and 30 participants in the control group not exposed to industrial vibration and healthy according to medical examination. The levels of pro-inflammatory (IL-1β, IL-8, TNF-α) and anti-inflammatory cytokines (IL-4) and the biomark ers of endothelial damage (EDN1, TGF-β1, VEGF-A, PDGF-BB, fibronectin, and von Willebrand factor) were determined by enzyme immunoassay. Results. The response of the immune system to the effects of industrial vibration is characterized by a cytokine imbalance — an increase in the level of pro-inflammatory cytokines (IL-1β, IL-8, TNFα) and a decrease in the level of anti-inflammatory cytokine (IL-4). With a combined course of vibration disease and arterial hypertension, the cytokine imbalance is characterized by an even more significant increase in serum concentration of IL-1β, IL-8, TNFα and a decrease in serum IL-4 concentration. Endothelial dysfunction in vibration disease from the exposure to both local and general vibration in combination with arterial hypertension is characterized by a significant increase in the serum concentration of EDN1, TGF-β1, VEGF-A, PDGF-BB, fibronectin, and von Willebrand factor. Conclusion. The study of the cytokine profile and biomarkers of damage to the vascular endothelium in this pathology will allow making early diagnosis of vascular disorders and optimizing preventive measures for workers in vibration hazard industries.

Effects of grape seed proanthocyanidin extract on side effects of high-dose methylprednisolone administration in male rats.

In this study, we investigated the effects of grape seed proanthocyanidin extract (GSPE) against the side effects of high-dose administration of methylprednisolone (MP) in male rats. A total of 32 adult Wistar male albino rats were divided into four groups: (1) control (CON), received standard food only; (2) MP, received standard food + intraperitoneal injection of 60mg/kg MP on day 7; (3) GSPE, received standard food + 200mg/kg/day GSPE; and (4) MP + GSPE, received standard food + 200mg/kg/day of GSPE + intraperitoneal injection of 60mg/kg MP on day 7. All animals in the GSPE and GSPE + MP groups were treated once a day by oral gavage for 14 consecutive days. The feed intake of rats in the MP and MP + GSPE groups decreased significantly by 24.14% and 13.52%, respectively (p < 0.05). Administration of MP resulted in significant increases in serum concentrations of blood urea nitrogen (p < 0.001), glucose (p < 0.01), alkaline phosphatase, and adrenocorticotropic hormone (p < 0.05). High-dose MP administration significantly reduced catalase (p < 0.001) and glutathione peroxidase (p < 0.05) concentrations in the liver and kidney tissues of rats, while glutathione concentrations were only reduced in liver tissue (p < 0.05). The expression levels of Bcl-2 and TNF-α in liver, kidney, and testicular tissue were significantly increased, while the expression levels of caspase-3 were reduced (p < 0.001). Furthermore, sperm concentration was significantly affected by GSPE in rats induced by high-dose MP, and sperm loss was significantly reduced in MP + GSPE (p < 0.05). These findings suggest that GSPE could be useful as a supplement to alleviate MP-induced toxicity in rats.

Feline precision medicine using whole-exome sequencing identifies a novel frameshift mutation for vitamin D-dependent rickets type 2.

A 14-week-old female domestic longhair kitten presented with shifting lameness and disproportionately smaller size compared with a co-housed littermate. Hematology and serum biochemical testing were conducted to investigate causes for delayed growth, and radiographs of the appendicular skeleton were obtained. The afflicted kitten had marked hypocalcemia, mild hypophosphatemia and substantial elevations in alkaline phosphatase activity, as well as pathognomonic radiographic findings consistent with rickets. Skeletal changes and hypocalcemia prompted testing of concentrations of parathyroid hormone (PTH) and vitamin D metabolites. Endocrine testing demonstrated significant increases in serum concentrations of PTH and 1,25-dihydroxycholecalciferol (calcitriol), supporting a diagnosis of vitamin D-dependent rickets type 2. Provision of analgesia, supraphysiologic doses of calcitriol and calcium carbonate supplementation achieved normalization of the serum calcium concentration and restoration of normal growth, although some skeletal abnormalities persisted. Once skeletally mature, ongoing calcitriol supplementation was not required. Whole-exome sequencing (WES) was conducted to identify the underlying DNA variant. A cytosine deletion at cat chromosome position B4:76777621 in VDR (ENSFCAT00000029466:c.106delC) was identified and predicted to cause a stop codon in exon 2 (p.Arg36Glufs*18), disrupting >90% of the receptor. The variant was unique and homozygous in this patient and absent in the sibling and approximately 400 other cats for which whole-genome and whole-exome data were available. A unique, heritable form of rickets was diagnosed in a domestic longhair cat. WES identified a novel frameshift mutation affecting the gene coding for the vitamin D3 receptor, determining the likely causal genetic variant. Precision medicine techniques, including whole-exome and whole-genome sequencing, can be a standard of care in cats to identify disease etiologies, and to target therapeutics and personalize treatment.

Individualised adjuvant immunotherapy with neoantigen-reactive T cells for gastric signet-ring cell carcinoma.

The signet-ring cell carcinoma (SRCC) of the stomach is highly invasive. Patients with stage III gastric SRCC usually experience tumor recurrence within 2 years after radical surgery. Unfortunately, there is no effective treatment to postpone recurrence following adjuvant chemotherapy. Our study aimed to explore the safety and efficacy of neoantigen-reactive T lymphocytes (NRTs) in patients with stage III gastric SRCC. The study included 20 patients with stage III gastric SRCC who received radical surgery and adjuvant chemotherapy. Following the adjuvant chemotherapy, they underwent treatment with a range of one to four cycles of personalised neoantigen-reactive T cells. The primary endpoint was the median progression-free survival (mDFS). The secondary endpoint was safety and immune responses. The median duration of follow-up was 41 months (95% CI: 39-42.9 months). Our results showed that patients who received adjuvant neoantigen-reactive T-cell immunotherapy demonstrated a propensity towards prolonged disease-free survival (DFS) and overall survival (OS) in comparison to previous studies. The 2-year DFS and OS rates reached 73.7% and 95%, respectively, whereas the 5-year DFS and OS rates were 44%and 69%. The median DFS was 41 months (95% CI: 28.9-53.1 months) and the median OS was not reached. In addition, there was a significant increase in serum concentrations of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ after cell immunotherapy. The adverse reactions were mild. In conclusion, adjuvant immunotherapy with NRTs showed promising efficacy alongside a manageable safety profile.

Extracellular inflammasome specks are released after marathon running and induce proinflammatory effects in endothelial cells

Abstract Objectives The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that inflammasome particles can be released into the circulation. The effects of exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) particles and their effects on endothelial cells are not known. Methods We established a flow cytometric method to quantitate extracellular ASC specks in human serum. ASC specks were quantitated in 52 marathon runners 24–72 hours before, immediately after, and again 24–58 hours after the run. For mechanistic characterization, NLRP3 inflammasome particles were isolated from a stable mutant NLRP3 (p.D303N)-YFP HEK cell line and used to treat primary human coronary artery endothelial cells (HCAEC). Results Athletes showed a significant increase in serum concentration of circulating ASC specks immediately after the marathon (t1, +52% compared to baseline, p&amp;lt;0.05) and a decrease during follow-up after 24–58 hours (t2, 12% reduction compared to immediately after the run, p&amp;lt;0.01). Confocal microscopy revealed that HCAEC can internalize extracellular NLRP3 inflammasome specks. After internalization, endothelial cells showed an inflammatory response with higher expression of the cell adhesion molecule ICAM1 (6.9-fold, p&amp;lt;0.05) and increased adhesion of monocytes (1.5-fold, p&amp;lt;0.05). Conclusion These findings identify extracellular inflammasome specks as novel systemic mediators of cell-cell communication that are transiently increased after acute high-intensity exercise. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): University Hospital Leipzig

Study of Many Biochemical and Oxidative Stress Variables in Patients with Atherosclerosis in Kirkuk City

The current study was designed to detect the role of a number of chemical variables represented by fasting blood sugar, hemoglobin A1c and insulin and oxidative stress factors in atherosclerosis patients. The present study involved (70) blood samples aged between (35-65) years the first group involved (40) blood samples from atherosclerosis patients and the second group involved (30) blood samples from healthy individuals, the samples were collected from respondents at Kirkuk General Hospital and Azadi Teaching Hospital in Kirkuk for a while 2021/12/22 to 2022/2/8 and the samples were taken after eight hours of fasting and all the information was taken from the reviewers by means of a questionnaire that included age, body mass index, systolic pressure and diastolic pressure and the results were as follows: significant increase in body mass index in the group of atherosclerosis patients compared to a healthy control group at a significant level (p 0.05) and 55% of them had elevated systolic pressure rate and 40% of them had high diastolic pressure ,the results from the current study show a significant increase in the concentration of asprosin compared to the control group at a significant level (p 0.05),the results of cardiac troponin(t) show a significant increase in the concentration of troponin in the patients of atherosclerosis compared to the control group at a significant level (p 0.05).&#x0D; The results of the study biochemical variables have shown significant increase in fasting blood sugar in the group of atherosclerosis patients compared to a control group at a significant level (p 0.05) and the results of glycated hemoglobin Test (A1c) showed a significant increase in the group of atherosclerosis patients compared to a control group at a significant level (p 0.05) and the results of insulin showed a significant increase in the group of atherosclerosis patients compared to a control group at a significant level (p 0.05).&#x0D; While the results of the study of the oxidative stress which included the glutathione and malondialdehyde there was insignificant reduction in serum concentration of GSH in atherosclerosis patients at a significant level (p 0.05) compared to a control group, and it has also been noted that was a significant increase in serum concentration of MDA in the atherosclerosis patients compared to a control group at a significant level (p 0.05).

Prognostic MicroRNA Panel for HCV-Associated HCC: Integrating Computational Biology and Clinical Validation.

Simple SummaryHepatocellular carcinoma (HCC) is a disease of poor prognosis. The early diagnosis of HCC will restrain the disease progression and thus improve patients’ quality of life. We aimed in this study to define a panel of microRNAs (miRNAs) that could facilitate the early prognosis of HCC focal lesions in the cirrhotic livers of patients previously infected with hepatitis C virus (HCV). A minimally invasive technique was used to measure the differential expression of isolated miRNAs from the serum of 201 HCV infected and HCV-HCC patients. We suggest that a panel of five serum miRNAs (miR-150, miR-199a, miR-224, miR-424, and miR-3607) might provide a potentially promising tool in the prognosis of HCC disease in cirrhotic HCV patients.Early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this widely spread disease. Dysregulation in microRNA (miRNA) expression is associated with HCC progression. The objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using a bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE-miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424, and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV, and 72 HCV-associated-HCC patients using real-time PCR (qPCR). There was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. A panel of five miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity). These preliminary data show that the novel miRNAs panel (miR-150, miR-199a, miR-224, miR-424, and miR-3607) could serve as a potential non-invasive biomarker for HCC early prediction in chronic HCV patients. Further prospective studies on a larger cohort of patients should be conducted to assess the potential prognostic ability of the miRNAs panel.

Marker of schizophrenia with enduring negative symptoms

IntroductionThe relevance of this study is determined by the need to search for biological markers of schizophrenia. The detection and validation of such molecules can become the basis for the creation of additional paraclinical diagnostic methods or contribute to the creation of targets for individual pharmacotherapy, which is an important task of modern fundamental medicine.ObjectivesComparative proteomic analysis of serum in schizophrenic patients with positive and negative symptoms.MethodsThe study includes 10 healthy donors and 27 patients with schizophrenia. Samples preparation included: serum purification from major proteins via affinity chromatography, 1D-PAGE proteins separation, in-gel tryptic hydrolysis, LC-MS/MS mass-spectrometry (Orbitrap Q-exactive HF mass spectrometer, Agilent Technologies). Identification of proteins was carried out using Mascot software Ver. 2.1 («Matrix Science», USA). Proteins for quantitative analysis were selected in view of the DISGENET database. Quantitative LC-MS-SRM analysis of selected protein was performed on QQQ TSQ Vantage (Thermo Scientific) with labeled peptide standards.ResultsReceptor-interacting serine/threonine-protein kinase 1 was selected for quantitative assessment. Significant differences were revealed in the RIPK1 concentrations in the serum of schizophrenic patients with negative and positive symptoms (p=0.02). The serum concentration of RIPK1 in patients with negative symptoms is tenfold in patients with positive symptoms.ConclusionsReceptor-interacting serine/threonine-protein kinase 1 can be considered a biomarker of negative symptoms of schizophrenia based on a significant increase in serum concentration. Mass spectrometric analysis was carried out of the “Human Proteome” Core Facility of the Institute of Biomedical Chemistry Moscow. Support by Grant of RSF № 18-15-00053P.DisclosureNo significant relationships.

Extracellular Inflammasome Particles Are Released After Marathon Running and Induce Proinflammatory Effects in Endothelial Cells.

Objectives: The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that inflammasome particles can be released into circulation. The effects of exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) particles and their effects on endothelial cells are not known. Methods: We established a flow cytometric method to quantitate extracellular ASC specks in human serum. ASC specks were quantitated in 52 marathon runners 24–72 h before, immediately after, and again 24–58 h after the run. For mechanistic characterization, NLRP3 inflammasome particles were isolated from a stable mutant NLRP3 (p.D303N)-YFP HEK cell line and used to treat primary human coronary artery endothelial cells. Results: Athletes showed a significant increase in serum concentration of circulating ASC specks immediately after the marathon (+52% compared with the baseline, p < 0.05) and a decrease during the follow-up after 24–58 h (12% reduction compared with immediately after the run, p < 0.01). Confocal microscopy revealed that human endothelial cells can internalize extracellular NLRP3 inflammasome particles. After internalization, endothelial cells showed an inflammatory response with a higher expression of the cell adhesion molecule ICAM1 (6.9-fold, p < 0.05) and increased adhesion of monocytes (1.5-fold, p < 0.05). Conclusion: These findings identify extracellular inflammasome particles as novel systemic mediators of cell–cell communication that are transiently increased after acute extensive exercise with a high mechanical muscular load.

Cytokine markers of clinical variants of infective endocarditis

Introduction. Infective endocarditis is a bacterial disease. Pathogen is localized mainly on heart valves and endocardium. This condition is accompanied by immunopathological manifestations and potential generation of septic process being unfavorable prognosis for disease outcome. Currently, the causes of death of patients with endocarditis have been increasingly presented as thromboembolic complications, which severity depends on variant of the disease course. An important role in imbalanced immune system in the infectious process is assigned to altered intercellular interaction mediated via cytokine network. Activated immune cells produce cytokines, which investigating is important in terms of interpreting changes in immune system functionality, assessing the severity of diseases and controlling therapeutic effectiveness. Infective endocarditis remains a severe disease associated with high mortality despite current advances in diagnostics and treatment. A timely diagnostic process and early initiation of treatment are major factors for successful patient management necessitating to improve diagnostics of various clinical variants of endocarditis course, taking into account pathogenetically relevant cytokines. Objective was to comparatively evaluate the importance of serum cytokine concentrations in patients with uncomplicated course of infective endocarditis and its thromboembolic complications and determine cytokine markers of various variants of endocarditis course. Materials and methods. An immunological examination of 119 blood serum samples from patients with confirmed diagnosis of infectious endocarditis and 20 samples from apparently healthy persons was carried out. Depending on the clinical disease form, the patients were divided into 4 groups: group 1 primary infective endocarditis (PIE) with thromboembolic complications (n = 24), 2 PIE without thromboembolic complications (n = 34), 3 secondary IE with thromboembolic complications (n = 27), 4 secondary IE without thromboembolic complications (n = 34). The control group consisted of 20 apparently healthy subjects. Immunological studies of serum cytokine concentrations were conducted in all groups. Results. Statistically significant increase in serum concentration of IL-10, IL-6, VEGF-A, IL-18, IL-1Ra and IL-8 was revealed in all clinical groups of patients compared to those in control group (p 0,05). By correlation analysis, we found a significant positive relationship between IL-10 and IL-18 or IL-6. An increase in the concentration of IL-10 leads to increased level of pro-inflammatory IL-18 and IL-6. The marker of secondary endocarditis was observed as increased level of serum concentrations of IFN. A characteristic feature of primary infective endocarditis with thromboembolic complications was revealed as significantly increased serum concentration of IL-8, IL-1Ra and IL-6. Markers of secondary complicated endocarditis were identified as increased level of IL-6, VEGF-A and IL-18.

Lead exposure-induced changes in hematology and biomarkers of hepatic injury: protective role of TrévoTM supplement.

Lead exposure has been linked to health challenges involving multiple organ failure. More than fifty percent of lead present in the human body is accumulated in the liver causing hepatic injury. A major mechanism of lead toxicity is oxidative stress. Trévo™ is a nutritional supplement with numerous bioactive natural products with detoxifying and antioxidant properties. This study was designed to investigate the hepatoprotective effects of Trévo™ dietary supplements against lead-hepatotoxicity in male Wistar rats. Thirty-five healthy animals were divided into five groups of seven each as follows: Group I=control; II=15 mg/kg of lead acetate (PbA); III= 2 mL/kg of Trévo™ + PbA; IV= 5 mL/kg of Trévo™ + PbA;V=5 mL/kg of Trévo™. Animals were orally treated with Trévo™ for two days before co-administration with PbA intraperitoneally for 12 consecutive days. Animals were sacrificed 24 h after the last administration and blood were collected via cardiac puncture and processed for hematological parameters and assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB). The liver was excised and processed for markers of oxidative stress and histopathological examination. Intraperitoneal administration of 15 mg/kg of PbA caused a significant increase in serum concentration of AST, ALT, while the concentration of ALB was significantly decreased (P<0.001). PbA caused a significant reduction in packed cell volume, hemoglobin while the total white blood cell count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils were increased. Oxidative stress was significantly pronounced in the liver of rats exposed to PbA as observed in the high concentration of malonedialdehyde, decreased concentration of glutathione, the activity of catalase, superoxide dismutase, and glutathione-S-transferase. Pretreatment with Trévo™ was able to significantly prevent the anemic, oxidative damage, and hepatic injury initiated by PbA. Histological examination also corroborated the biochemical results. In conclusion, the study reveals that Trévo™ is effective in attenuating PbA-induced hepatotoxicity in male Wistar rats.

Immunological role of cluster of differentiation 56 and cluster of differentiation 19 in patients infected with mycobacterium tuberculosis in Iraq

Tuberculosis (TB) is one of the most dangerous infection mainly caused by gram positive bacteria Mycobacterium tuberculosis (Mtb) and cause many deaths every year worldwide especially in developing countries and activate the humoral and cellular immune response. The aim of this study was to investigate the role of CD56 and CD19 as diagnostic and immune markers in patients infected with Mtb. A total number of 26 patients infected Mtb and 27 patients infected with Multi-Drug resistance Mtb (MDR-Mtb) and 30 healthy individuals were included in this study. Mtb has been diagnosed by acid fast stain and MDR-Mtb were diagnosed by GeneXpert® heminested real time PCR for simultaneous detection of Mtb and rifampicin (RIF) resistance as MDR-Mtb. Serum concentration of CD56 and CD19 has been measurement by Enzyme-Linked Immune-sorbent Assay (ELISA) method. Results of this study showed a significant increase in the serum concentration of CD56 (P value = 0.0001) in Mtb-patients (1.95 ± 0.08 ng/ml) as compared with healthy individuals (1.17 ± 0.09 ng/ml). The same significant increases in the serum concentration of CD56 (2.24 ± 0.12 ng/ml) was reported in MDR-Mtb patients as compared to the healthy individuals. On the other hand, there was significant increase (P value 0.003) in serum concentration of CD19 in Mtb-patients as compared with MDR-Mtb-patients. Results of the study can be concluded that Mtb and MDR-Mtb infection stimulates the cellular and humoral immune response which resulted in the increased production of CD56 and CD19.

Primary sclerosing cholangitis in children with inflammatory bowel disease

Introduction. Currently, in pediatric practice, there are no clear data on the features of the onset of primary sclerosing cholangitis (PSC) in inflammatory bowel diseases (IBD), the frequency of detection of markers of cytolysis and cholestasis, the nature of the lesion of the hepatobiliary system and changes in the endoscopic picture. Purpose: assessment of clinical, laboratory, and instrumental features of PSC course in IBD children (PSC+IBD). Materials and methods. For the period 2015-2021, a comprehensive examination of 54 children with PSC+IBD (main group) and 79 patients with isolated IBD (comparison group): ulcerative colitis (UC) or Crohn’s disease (CD) was carried out. Results. In 54 children of the main group, the combination of PSC+UC was detected in 48 (88.9%) patients with a predominance of boys. At the onset of the disease, the most frequent manifestations in children with PSC+IBD were diarrhea, abdominal pain syndrome, cytolysis and cholestasis syndromes, and hemocolitis. In children with PSC+IBD, compared with patients with IBD, there was a statistically significant increase in serum concentrations of ALT, AST and total protein, indicating an increase in hepatitis activity; GGT, alkaline phosphatase and direct bilirubin - about an increase in the severity of cholestasis syndrome; IgG - as a marker of the severity of mesenchymal-inflammatory syndrome in the framework of liver damage. According to the endoscopic data, with PSC+UC, pancolitis with more pronounced involvement of the right colon or isolated proctitis prevails, and with PSC+CD, ileocolitis is more common. Indices PUCAI (p &lt; 0.001) and PCDAI (p = 0.027) were statistically significantly lower in the PSC+IBD group than in the isolated IBD. According to the data of transient liver elastometry, no statistically significant difference was obtained between the medians of the parameters of the biochemical blood test at different stages of fibrosis. According to the results of magnetic resonance imaging of the abdominal organs and MR-cholangiopancreatography, the most characteristic changes in PSC+IBD are heterogeneity of the liver parenchyma, unevenness of the intra- and extrahepatic bile ducts, the presence of areas of expansion and narrowing of their diameter. Conclusions. The phenotype of PSC+IBD in children is manifested mainly by intestinal symptoms, more often UC with involvement of the right parts of the intestine in boys and a lower activity index than the isolated course of IBD, in combination with laboratory syndromes and cholestasis.