Serum Concentrations Of Protein Research Articles

Impact of PSDS Combined with Ganciclovir on Treatment and Serum C5 with Inflammation and Oxidative Stress in Serum and Tears of Herpes Simplex Keratitis Patients

Background: Herpes simplex virus (HSV) is a well-established cause of eye disease and associated blindness. It is known as herpes simplex keratitis (HSK) when the HSV invades the cornea and causes symptoms such as eye pain and dryness, lacrimation, and impaired vision. Objectives: To investigate the therapeutic effect of potassium sodium dehydroandroandrographolide succinate (PSDS) combined with ganciclovir in patients with HSK. Methods: Herpes simplex keratitis patients (n = 80) were randomized into two groups (control group and ganciclovir + PSDS group). Treatment efficacy was recorded. The changes in serum C5 and concentrations of inflammatory and oxidative stress factors in the serum and tears were compared. The correlations between changes in serum C5 concentration and changes in high-sensitivity C-reactive protein (hs-CRP) and superoxide dismutase (SOD) concentrations in serum and tears were analyzed. Results: The treatment efficacy was better in the ganciclovir + PSDS group. Serum C5 concentration was lower in the ganciclovir + PSDS group after treatment. In addition, the concentrations of hs-CRP and tumor necrosis factor-α (TNF-α) as well as malondialdehyde (MDA) and SOD in the serum and tears were also lower in the ganciclovir + PSDS group. Serum C5 concentration was positively correlated with hs-CRP concentration and negatively associated with SOD concentration. Conclusions: We found improvements in clinical symptoms of patients treated with ganciclovir + PSDS. Our results suggest that the addition of PSDS to ganciclovir treatment will effectively reduce inflammation and oxidative stress and relieve the clinical symptoms of patients with HSK.

Evaluating TAB2, IKBKB, and IKBKG Gene Polymorphisms and Serum Protein Levels and Their Association with Age-Related Macular Degeneration and Its Treatment Efficiency

Background: Age-related macular degeneration (AMD) is the leading cause of blindness, affecting millions worldwide. Its pathogenesis involves the death of the retinal pigment epithelium (RPE), followed by photoreceptor degeneration. Although AMD is multifactorial, various genetic markers are strongly associated with the disease and may serve as biomarkers for evaluating treatment efficacy. Objective: This study investigates TAB2 rs237025, IKBKB rs13278372, and IKBKG rs2472395 variants and their respective serum protein concentrations in relation to AMD occurrence and exudative AMD treatment response to anti-VEGF treatment. Results: Our study revealed that TAB2 rs237025 allele A was identified as a risk factor for early and exudative AMD development. The same associations remained only in females with exudative AMD but not in males, suggesting gender-specific pathogenetic pathways in exudative AMD. Analysis of IKBKB rs13278372 or serum IKBKB protein associations with early or exudative AMD occurrence in the Lithuanian population revealed no significant associations. On the other hand, we found that each A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment (OR = 0.347; 95% CI: 0.145–0.961; p = 0.041). These results suggest a potential marker for future studies evaluating anti-VEGF treatment for exudative AMD patients. IKBKG rs2472395 was a protective variant for early AMD in males and for exudative AMD in females only. Also, IKBKG protein concentration was lower in exudative AMD relative to the control group (median (IQR): 0.442 (0.152) vs. 0.538 (0.337), p = 0.015). Moreover, exudative AMD patients who carry the GG genotype of IKBKG rs2472394 exhibited significantly reduced serum IKBKG concentrations compared to the controls (median (IQR): 0.434 (0.199) vs. 0.603 (0.335), p = 0.012), leading to the hypothesis that the IKBKG rs2472394 variant might play a role in protein concentration differences and exudative AMD development. Conclusions: Our study identified the TAB2 rs237025 allele A as a significant risk factor for both early and exudative AMD, with gender-specific associations observed in females with exudative AMD, suggesting distinct pathogenetic pathways. While IKBKB rs13278372 and serum IKBKB protein levels showed no significant association with AMD development, the A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment, indicating its potential as a marker for treatment outcomes. Additionally, the IKBKG rs2472395 variant was found to be protective for early AMD in males and exudative AMD in females, and lower IKBKG protein levels were associated with exudative AMD, particularly in patients with the GG genotype of IKBKG rs2472394, suggesting its role in protein concentration and disease progression. These findings highlight genetic markers that may contribute to AMD pathogenesis and treatment response.

Brain changes following subchronic exposure to copper oxide nanoparticles: animal experimental data analysis

AbstractThe goal of this study was to assess the health effects of (copper oxide nanparticles) CuO NPs on the brain structure and function in rats. Morphology results showed that the number of axons with the damaged myelin sheath in basal ganglia and the proportion of pathologically altered mitochondria in olfactory bulbs and basal ganglia had increased, while the concentration of myelin basic protein in blood serum remained unchanged. We also have observed the lower body weight gain, signs of hemolytic anemia, an increased platelet count, reduced locomotion and exploratory activity. We propose that the central nervous system and haematopoiesis are the targets for toxicity of CuO NPs administered intranasally during six weeks at the total dose of 0.45 mg/kg body weight.

An automated blood test for glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) to predict the absence of intracranial lesions on head CT in adult patients with mild traumatic brain injury: BRAINI, a multicentre observational study in Europe

Following mild traumatic brain injury (mTBI), elevated concentrations of brain-specific blood proteins glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) may be indicative of intracranial lesions normally detected by head CT scans. We sought to validate the performance of this combination of biomarkers at predetermined cutoff values with an automated immunoassay to predict which patients did not have intracranial lesions. This prospective, observational study was conducted in France and Spain at 16 emergency departments. Adult patients with mTBI were eligible if they had a head CT scan and gave a 10-ml blood sample within 12h of injury. GFAP and UCH-L1 serum concentrations were measured and analysed, in less than an hour time, according to predefined cutoff values of 22pg/ml and 327pg/ml, respectively. Serum concentrations of S100B protein were concomitantly determined in a subset of patients. The primary outcome measures were the sensitivity and negative predictive value (NPV) of the combined GFAP-UCH-L1 test to rule out intracranial lesions on head CT scans. gov (NCT04032509). Between August 2019 and June 2021, 1508 patients were recruited, and 1438 were included in the main analysis. Median age was 69 years (IQR 44-83). Most patients (74%) presented 3h after trauma. 179 (12.4%) patients were positive for intracranial lesions by CT. The sensitivity of the combined test was 98.3% (95% CI 95.0-99.7) and the specificity 24.9 (95% CI 22.6-27.4), with a NPV of 99.1% (95% CI 97.1-99.8). Three patients with a positive CT scan had negative biomarker test results. S100B had a sensitivity of 83.0% (95% CI 76.2-88.2) and a NPV of 94.2% (95% CI 91.6-96.0). Patients with higher biomarker values more frequently had poorer recovery at 3 months after injury. Testing for GFAP and UCH-L1, using validated cutoffs obtained with a new, fast automated immunoassay platform, accurately predicted the absence of intracranial lesions on head CT following mTBI. This study is co-funded by the European Institute of Innovation and Technology (EIT) Health, a body of the European Union (Grant nº19474). Biomarkers tests were funded by bioMérieux.

Effects of Bacterial Enzyme Cooperative Fermentation Diet on Growth Performance, Blood Biochemical Indices, and Fecal Microflora of Growing–Finishing Pigs

This research utilized Fourier transform infrared (FTIR) spectroscopy to analyze and discuss the molecular structure of pig diets, aiming to provide new insights into the application of fermented feeds in livestock and poultry production. Moreover, the impacts of the fermented diet on growth performance, apparent digestibility, blood biochemical indices, and fecal microorganisms at different stages of pig fattening were also explored. Forty-eight pigs (Duroc × Landrace × Large white three-way hybrid) with a mean body weight of 16.55 ± 3.88 kg were randomly divided into three groups with four replicates per group and four pigs per replicate. The control group was fed a basal diet. The pigs in the fermented diet group (T1) were fed Pediococcus acidilactici (PA), Lactobacillus reuteri (LR), and Bacillus velezensis (BS) (ratio of 1:1:1) at a 6% inoculation dose. The pigs in the cooperative fermentation group (T2) were fed 6% PA, LR, BS, and a 0.2% compound enzyme preparation. The T1 and T2 diets were fermented with 45% water at 33 °C for 48 h. The pre-feeding period lasted 7 days, and the experimental period lasted 84 days. The experimental results showed that the bacterial enzyme cooperation fermentation process significantly increased the contents of crude protein, calcium, and phosphorus in the diet; increased the area of amide Ⅰ region; increased the apparent digestibility of neutral detergent fiber and phosphorus; significantly increased average daily gain; and decreased the feed-to-gain ratio in the late fattening and growth period. During the whole experiment, the serum concentrations of total protein and immunoglobulin A were significantly increased, the serum concentrations of superoxide dismutase and glucose were decreased, and the diversity and richness of fecal microorganisms were increased. These results show that the bacterial enzyme cooperative fermentation diet can improve the apparent digestibility of nutrients and improve overall health by increasing the area of amide Ⅰ region.

The association between adipokines dysregulation and the occurrence of atrial fibrillation and obese patients, is it relevant?

Atrial fibrillation (AF) is the most common arrhythmia, affecting approximately 33.5 millions of people worldwide. Unfortunately, the prevalence of this arrhythmia will increase within the following two decades, resulting in a higher mortality rate and a higher economic burden for public health services. Obesity, specifically central obesity, plays an essential role in developing AF by increasing pericardial fat and epicardial adipose tissue thickness, generating a chronic inflammation state where dysregulation of the serum concentration of several proinflammatory proteins occurs and indirectly promotes AF. Therefore, recent research has focused on analyzing the circulating concentration of different molecules, including pro and anti-inflammatory adipokines, and their association with AF. Herein, we review several studies addressing the association of adipokines with the onset or recurrence of AF to establish such association as a potential biomarker for the prevention or adequate treatment of this arrhythmia. We concluded that the insight into this topic is very controversial and needs further research.

Systemic immune-inflammation mediates the association between Klotho protein and metabolic syndrome: findings from a large-scale population-based study.

This study utilized large-scale population data from the National Health and Nutrition Examination Survey (NHANES) to elucidate the relationship between the Klotho protein and metabolic syndrome along with its components. We further investigated the possible mediating effect of inflammation on these relationships. Our objective was to identify biomarkers for risk stratification and potential therapeutic targets for metabolic syndrome. This study enrolled 13,119 participants aged 40-79 years, spanning five NHANES cycles from 2007 to 2016, with complete information on metabolic syndrome and the Klotho protein. The definition of metabolic syndrome followed the criteria of the National Cholesterol Education Program-Adult Treatment Panel III. Survey-weighted logistic regression and subgroup analysis were used to explore the associations between serum Klotho protein levels and metabolic syndrome, along with its components. Mediation analysis was performed to investigate the mediating effects of inflammation-related markers, including white blood cells, neutrophils, lymphocytes, monocytes, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) and the monocyte-to-HDL ratio (MHR), with the aim of elucidating how the Klotho protein influences the onset and progression of metabolic syndrome. The study participants had an average age of 56.06 years (95% CI: 55.76-56.37), with a Klotho protein concentration of 798.10 pg/ml (95% CI: 656.50-980.50) and a 43.77% prevalence of metabolic syndrome (n = 5742). In the crude model, Klotho was negatively correlated with metabolic syndrome and its components, including central obesity, hypertension, and hypertriglyceridemia. After adjusting for all confounding factors, Klotho was demonstrated to be negatively associated only with metabolic syndrome (OR: 0.82, 95% CI: 0.70-0.97), hypertension (OR: 0.83, 95% CI: 0.70-0.98), and hypertriglyceridemia (OR: 0.78, 95% CI: 0.67-0.91). Subgroup and interaction analyses revealed significant interactions between age, sex, race/ethnicity, body mass index, and Klotho. Additionally, mediation analysis demonstrated that leukocytes, neutrophils and monocytes accounted for 34.78%, 31.91% and 7.13%, respectively, of the associations between Klotho and metabolic syndrome. The serum concentration of Klotho protein was negatively associated with metabolic syndrome, with the relationship being partly mediated by systemic immune inflammation. The findings of this research revealed that the Klotho protein may be a valuable biomarker for risk stratification and a potential therapeutic target for metabolic syndrome.

Influenza and non-influenza ARVI in children. A relationship between cytokine profile, parameters of the “lipid peroxidation – antioxidant defense system” as well as clinical and laboratory indicators

Influenza and acute respiratory viral infections (ARVI) impose a substantial damage to the population health in the Russian Federation due to their seasonal circulation and predominantly affect young children. A very few data on the cytokine profile, the nonspecific LPO — AOD system and their relationships with clinical characteristics in such diseases in preschool children are available. The aim of this study was to assess the cytokine profile, LPO — AOD system parameters and their relationship with the clinical and laboratory characteristics of diseases in preschool children with influenza and other ARVI. 86 preschool children (3–6 years old) were examined: with an established diagnosis of influenza (n = 31), non-influenza ARVI (n = 28), apparently healthy children (control group (n = 27). All pediatric samples were analyzed by enzyme-linked immunosorbent assay assessing blood serum concentrations of C-reactive protein and cytokines IL-1β, IL-4, IL-6, IL-8, TNFα, IFNα, IFNγ. Spectrophotometric, fluorometric and enzyme immunoassay methods to assess the state of the “LPO — AOD” system were used. In the group of children with influenza vs other ARVI, a higher incidence of intoxication syndrome was revealed. Cytokine profile in children from both clinical groups compared with control cohort was featured with higher indicators of both pro-inflammatory and anti-inflammatory origin. Children with non-influenza ARVI, had increased magnitude of LPO final products in the nonspecific LPO — AOD system along with lowered concentration of fat-soluble vitamins, general antioxidant activity, GSH level, and SOD activity. In the group with influenza, the level of primary and final lipid peroxidation products was increased, whereas that of for retinol,α-tocopherol, and total antioxidant activity was decreased paralleled with higher GSSG and SOD levels. Numerous correlations were noted in the group of children with ARVI: IL-1β/ketones, IL-6/ketones, IL-8/ketones, TNFα/ketones, IL-4/ketones, IFNg/shortness of breath, IFNα/cough, double bonds/fever, double bonds/AST, SO/intoxication, retinol/fever, GSSG/cough. The influenza group differed in the following relationships: IL-4/ketones, IL-4/fever, IFNα/ketones, CDs/AST. It can be concluded that in preschool children with ARVI and influenza, changes in the cytokine profile are accompanied by increased pro- and anti-inflammatory cytokine levels, increased intensity of lipid peroxidation reactions along with reduced magnitude of antioxidant factors. In the group with ARVI, there was a relationship between the final toxic products of lipid peroxidation — Schiff bases — and the intoxication index, as well as the presence of protective mechanisms in the form of connections between interferons and disease clinical manifestations. The group with influenza was distinguished by the presence of protective relations, which may have a beneficial effect in the context of developing pathological process. The data obtained will help expand the understanding of the pathogenetic mechanisms related to immune reactivity and nonspecific lipid peroxidation reactions in preschool patients and formulate appropriate measures for correction.

Component Distribution, Shear-Flow Behavior, and Sol-Gel Transition in Mixed Dispersions of Casein Micelles and Serum Proteins.

The shear flow and solid-liquid transition of mixed milk protein dispersions with varying concentrations of casein micelles (CMs) and serum proteins (SPs) are integral to key dairy processing operations, including microfiltration, ultrafiltration, diafiltration, and concentration-evaporation. However, the rheological behavior of these dispersions has not been sufficiently studied. In the present work, dispersions of CMs and SPs with total protein weight fractions (ωPR) of 0.021-0.28 and SP to total protein weight ratios (RSP) of 0.066-0.214 and 1 were prepared by dispersing the respective protein isolates in the permeate from skim milk ultrafiltration and then further concentrated via osmotic compression. The partition of SPs between the CMs and the dispersion medium was assessed by measuring the dry matter content and viscosity of the dispersion medium after separating it from the CMs via ultracentrifugation. The rheological properties were studied at 20 °C via shear rheometry, and the sol-gel transition was characterized via oscillatory measurements. No absorption of SPs by CMs was observed in dispersions with ωPR = 0.083-0.126, regardless of the RSP. For dispersions of SPs with ωPR ≤ 0.21, as well as the dispersion medium of mixed dispersions with ωPR = 0.083-0.126, the high shear- rate-limiting viscosity was described using Lee's equation with an SP voluminosity (vSP) of 2.09 mL·g-1. For the mixed dispersions with a CM volume fraction of φCM ≤ 0.37, the relative high shear-rate-limiting viscosity was described using Lee's equation with a CM voluminosity (vCM) of 4.15 mL·g-1 and a vSP of 2.09 mL·g-1, regardless of the RSP. For the mixed dispersions with φCM > 0.55, the relative viscosity increased significantly with an increasing RSP (this was explained by an increase in repulsion between CMs). However, the sol-gel transition was independent of the RSP and was observed at φCM ≈ 0.65.

Personalized, disease-stage specific, rapid identification of immunosuppression in sepsis.

Data overlapping of different biological conditions prevents personalized medical decision-making. For example, when the neutrophil percentages of surviving septic patients overlap with those of non-survivors, no individualized assessment is possible. To ameliorate this problem, an immunological method was explored in the context of sepsis. Blood leukocyte counts and relative percentages as well as the serum concentration of several proteins were investigated with 4072 longitudinal samples collected from 331 hospitalized patients classified as septic (n=286), non-septic (n=43), or not assigned (n=2). Two methodological approaches were evaluated: (i) a reductionist alternative, which analyzed variables in isolation; and (ii) a non-reductionist version, which examined interactions among six (leukocyte-, bacterial-, temporal-, personalized-, population-, and outcome-related) dimensions. The reductionist approach did not distinguish outcomes: the leukocyte and serum protein data of survivors and non-survivors overlapped. In contrast, the non-reductionist alternative differentiated several data groups, of which at least one was only composed of survivors (a finding observable since hospitalization day 1). Hence, the non-reductionist approach promoted personalized medical practices: every patient classified within a subset associated with 100% survival subset was likely to survive. The non-reductionist method also revealed five inflammatory or disease-related stages (provisionally named 'early inflammation, early immunocompetence, intermediary immuno-suppression, late immuno-suppression, or other'). Mortality data validated these labels: both 'suppression' subsets revealed 100% mortality, the 'immunocompetence' group exhibited 100% survival, while the remaining sets reported two-digit mortality percentages. While the 'intermediary' suppression expressed an impaired monocyte-related function, the 'late' suppression displayed renal-related dysfunctions, as indicated by high concentrations of urea and creatinine. The data-driven differentiation of five data groups may foster early and non-overlapping biomedical decision-making, both upon admission and throughout their hospitalization. This approach could evaluate therapies, at personalized level, earlier. To ascertain repeatability and investigate the dynamics of the 'other' group, additional studies are recommended.

Comparative Evaluation of Lipid Profile, C-Reactive Protein and Paraoxonase-1 Activity in Dogs with Inflammatory Protein-Losing Enteropathy and Healthy Dogs.

Chronic inflammation alters lipoprotein metabolism and causes changes in the serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme that may act as a local detoxifier, antioxidant, and immunomodulator in the gastrointestinal tract. Scarce information is available in dogs with protein-losing enteropathy secondary to chronic enteropathy (iPLE). The first aim was to describe and compare the lipid profiles, CRP concentrations and PON-1 activities in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides and lipoprotein classes. Serum concentrations of albumin, total protein, cholesterol, PON-1 activity, and high-density and very-low-density lipoproteins were lower in iPLE dogs compared to healthy controls, while those of triglycerides, low-density lipoproteins, chylomicrons and CRP were higher. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. High-density and low-density lipoproteins correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. The results need to be confirmed in further studies.

Method of intensification of digestive and intermediary metabolism in meat quails during denitrification

Sorbents are characterized by synergistic action with many biologically active compounds, including antioxidants that neutralize free radicals in the body, prevent membrane damage, and preserve the youth of the cells of organs and tissues of poultry. The purpose of the study was to determine the eff ect of the sorbent Mikosorb®A Plus and the antioxidant Hadox on the parameters of digestive and intermediary metabolism in meat quails when they are added to compound feed with a subtoxic dose of nitrates. It was found that in order to improve the digestive and intermediary metabolism in meat quails, the composition of their compound feed should include the drugs of the sorbent Mikosorb®A Plus at the dose of 1000 g/t and the antioxidant Hadox at the dose of 150 g/t of compound feed. These drugs allowed to increase signifi cantly (p < 0.05) the coeffi cients of dry matter digestibility by 3.43 abs.%, organic matter by 3.33 abs.%, crude protein by 3.55 abs.%, crude fi ber by 3.48 abs.% and nitrogen-free extractive substances by 3.57 abs.% in the quails of the 3rd experimental group compared to the control group. This also allowed to increase the number of erythrocytes in the blood of quails of the 3rd experimental group by 0.56×1012/l (p < 0.05), hemoglobin by 7.0 g/l (p < 0.05) with a simultaneous decrease in methemoglobin by 1.40 % (p < 0.05) compared to the control analogues. In the quails of the 3rd experimental group, the concentration of total protein in the blood serum was higher by 5.20 g/l (p < 0.05) with a simultaneous decrease in the content of nitrates by 1.63 times (p < 0.05) and nitrites by 2.47 times (p < 0.05) compared to the quails of the control group. Joint feeding of the sorbent and antioxidant inhibited lipid peroxidation processes and had a stimulating eff ect on the antioxidant defense mechanism in the quail body. At the same time, the quails of the 3rd experimental group had a lower proportion of conjugated dienes by 40.54 % and malondialdehyde by 28.72 % compared to the control group.

Impact of dietary L-carnitine supplementation on blood parameters and duodenal alterations in laying hens at the end of production

L-carnitine is an important nutritional supplement in the poultry industry, contributing to improved growth, production, and overall health of the birds. However, by the end of the production cycle, the endogenous synthesis of L-carnitine (LC) is often insufficient. This study aimed to evaluate the effects of dietary L-carnitine supplementation on blood parameters and duodenal structure in Ross laying hens during the last production phase. A total of 40 Ross strain laying hens, aged 70 weeks, were selected. The control group was administered a basal diet, while the experimental groups received the same diet supplemented with 100, 250, or 500 mg of L-carnitine per kg of the basal diet. The experimental period lasted for 56 days. Serum concentrations of cholesterol and total protein were not significantly affected by L-carnitine supplementation; however, triglyceride concentration and LDL levels were notably reduced. Furthermore, L-carnitine supplementation enhanced the villus perimeter and increased the villus length/crypt depth ratio. Importantly, the supplementation of 250 mg/kg of L-carnitine had a positive impact on duodenum structure and led to decreased levels of AST and ALP. In conclusion, the incorporation of 250 mg/kg of L-carnitine into the diet of laying hens significantly improved duodenal structure, reduced lipid peroxidation, and demonstrated antioxidant effects.

Comparative assessment of neurotrophic proteins in vibration disease

Introduction. The problem of health impairment due to the impact of physical factors, including vibration disease (VD), retains medical and social relevance due to the significant specific gravity in the structure of occupational morbidity and high prevalence. Under vibration exposure, the acid-base equilibrium, immune status are disturbed, rheological properties and properties of the neurohumoral system, as well as functional indices of the central and peripheral nervous system change. Neurotrophins are known to play an important role in regulating the development and functioning of the central and peripheral nervous systems. In this regard, research is needed to determine in VD patients the levels of neurospecific proteins, which may serve as one of the markers for tracing changes in the nervous system in workers. The aim of the study was to identify the peculiarities of changes in neurospecific proteins (BDNF, S100β, and MBP) in the serum of patients with VD of different genesis. Materials and methods. Serum concentrations of neurotrophic proteins: brain neurotrophic factor – BDNF, S100β protein and myelin basic protein (MBP) were studied by solid-phase enzyme-linked immunoassay. Results. There was an increase in serum BDNF, S100β protein, and MBP concentrations in persons with VD due to combined exposure to local and general vibration, and an increase in MBP was observed in patients with VD due to exposure to local vibration. Limitations. The limitations of this work are small groups of employees. Conclusion. As a result of studies, it can be assumed that in VD due to exposure to combined vibration, changes are observed in the peripheral and central parts of the nervous system, and in VD due to local vibration, disorders seem to be mainly associated with the peripheral nervous system. The general pattern of the revealed disorders in the content of MBP lies in the neurodestructive processes occurring in the nerve fibers in patients with VD, regardless of genesis. Summarizing the above mentioned, the validity of studying the concentration of neurospecific proteins in vibration disease occurring with damaging processes in the nervous tissue should be recognized.

Evaluation of potential novel biomarkers for feline hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy in cats. The diagnosis can be difficult, requiring advanced echocardiographic skills. Additionally, circulating biomarkers (N-terminal pro-B type natriuretic peptide and cardiac troponin I) have several limitations when used for HCM screening. In previous work, we identified interleukin 18 (IL-18), insulin-like growth factor binding protein 2 (IGFBP-2), brain-type glycogen phosphorylase B (PYGB), and WNT Family Member 5 A (WNT5A) as myocardial genes that show significant differential expression between cats with HCM and healthy cats. The products of these genes are released into the circulation, and we hypothesized that IL-18, IGFBP-2, PYGB, and WNT5A serum RNA and protein concentrations differ between healthy cats, cats with subclinical HCM, and those with HCM and congestive heart failure (HCM + CHF).Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) and enzyme-linked immunosorbent assay (ELISA) were applied to evaluate gene and protein expression, respectively, in the serum of eight healthy controls, eight cats with subclinical HCM, and six cats with HCM + CHF. Serum IGFBP-2 RNA concentrations were significantly different among groups and were highest in cats with subclinical HCM. Compared to healthy controls, serum IL-18 and WNT5A gene expression were significantly higher in cats with HCM + CHF, and WNT5A was higher in cats with subclinical HCM. No differences were observed for PYGB.These results indicate that further investigation via large scale clinical studies for IGFBP-2, WNT5A, and IL-18 may be valuable in diagnosing and staging feline HCM.

B-102 The Impact of Protein / Protein Interactions on Serum Free Light Chain Assay Calibration

Abstract Background Since 2001, Serum Free Light Chain measurements have become established as routine clinical laboratory tests. Katzmann (2002) published a reference interval based on 282 normal samples establishing a ratio reference range 0.26-1.65. Whilst kappa and lambda measurements are of little diagnostic value, kappa/lambda ratio gives a strong indication of monoclonal gammopathy. In recent years, it has been suggested that the ratio may have changed. Here we present investigations identifying protein/protein interactions that may account for the discrepancies between QC release and real-world data; identifying a remediation step which will allow verification of the published ratio. Methods The manufacturers QC release data was reviewed for kappa, lambda and kappa/lambda ratio for all lots from 2018-2023, and compared to published data. To mimic field observation, an accelerated stability study was performed on standard calibrators and protein/protein interactions identified using western blot. Subsequently, calibrators were depleted of alpha-1 antitrypsin (A1AT) and other serum proteins using specific affinity chromatography; accelerated stability was repeated. A calibrator of pure polyclonal free light chains (FLC) in human serum albumin was produced in the presence/absence of A1AT and additional interfering serum proteins. Results At release, the average kappa reference range was 7.2-29.5 mg/L (62 kits, 9 different US blood donor sera collections and 3852 data points) and 7.7-24 mg/L for lambda (78 kits, 9 different US blood donor sera and 4664 data points), with a kappa/lambda ratio of 0.45-1.69. There was minimal change over 5yrs to these measurements. Analysis of FLC calibrators during an accelerated stability identified interactions between kappa FLC and ubiquitous serum proteins, including A1AT. The standard calibrator activity declined by 14.9±0.1% (mean±SEM) over a 4-month accelerated period @22oC, equivalent to 16 months real time. Calibrators depleted of A1AT and specific additional serum proteins showed significantly less decline in activity 1.4±1.4%, p<0.001. When blood donor sera were analysed using the standard calibrators following 4 months at 22oC, the results showed an increase in the reported kappa concentrations compared to those generated from frozen calibrators (19.0[15.4-22.5] to 21.3[17.0-26.0] mg/L, 12.5±3.8%, p<0.001). This observation was mirrored in kappa/lambda ratio (1.3[1.1-1.5] to 1.4[1.2-1.7] mg/L, 12.5±3.8%, p<0.001) and when clinical patient samples were assessed (30.1[14.0-47.1] to 34.3[15.5-56.9] mg/L, 13.8±1.4%, p<0.001). The depleted calibrator did not report an increase in sample results. FLC+HSA calibrators, when spiked with either physiological concentrations of A1AT or other serum proteins, showed a 16.7% and 15.3% decrease in activity respectively, compared to FLC+HSA calibrators without additional proteins. Conclusions At release, US blood donor sera have different absolute kappa mg/L compared to the published reference interval, but these changes do not invalidate the published kappa/lambda ratio, in contrast to recent reports and have not changed since 2018. An unpredictable kappa/protein interaction was observed, particularly with A1AT in a time dependent fashion, which correlated to a reduction in calibrator activity. Removal of A1AT and other specific serum proteins remediated the issue, and the kappa/lambda ratio was verified irrespective of the age of the calibrator.

A New Strain of Saccharomyces cerevisiae in Diets of Lactating Holstein Cows Improved Feed Efficiency and Lactation Performance

Abstract This study compared the effects of feeding a new strain of Saccharomyces cerevisiae HSA2020 with a commercial strain on in vitro rumen fermentation and production performance of dairy cows. Permeate was used as a substrate for the laboratory production of the new strain of S. cerevisiae after the hydrolysis by β-galactosidase (5000 µ/mL at 37°C). Two experiments were conducted: in Experiment 1, the effects of three levels (1, 2 and 3 g/kg dry matter) of S. cerevisiae on in vitro ruminal fermentation kinetics were evaluated. In Experiment 2, for 60 days, sixty multiparous Holstein cows (639±24.8 kg BW, 3±1 parity, 7±1 days in milk, with a previous milk production of 23±2.0 kg/d) during the previous lactation, were randomly assigned to 3 treatments in a completely randomized design. Cows were fed without any additives (control treatment) or supplemented with 2 g/kg feed daily of laboratory produced (PY) or commercial (CY) S. cerevisiae. In Experiment 1, inclusion of PY and CY increased (P<0.05) gas production, propionate, and nutrient disappearance, while decreased (P<0.05) methane production and protozoal count. Moreover, in Experiment 2, PY followed by CY increased (P<0.01) nutrient digestibility, and serum concentrations of total protein, albumin, and glucose (P<0.05). Higher daily milk yield, and milk energy output were observed with PY and CY without affecting concentrations of milk components or milk fatty acid profile. Compared to control, increased feed efficiency was observed with PY and CY. Compared to PY, CY increased serum concentrations of urea-N and decreased triglycerides, while PY decreased serum aspartate transaminase and increased concentration of conjugated linoleic acids in milk. In early lactating cow diets, both strains of S. cerevisiae improved production performance at 2 g/kg, and minimal differences between strains were found.

Synergistic Benefits of Dietary Silymarin and Selenium on Growth, Immune Functions, Antioxidants, and Gut/Liver Health of Thinlip Mullet (Liza ramada) Juveniles

Abstract This study investigates the synergistic impact of silymarin (SI) levels combined with inorganic selenium (sodium selenite: Se) on growth, feed utilization, biochemical parameters, antioxidants, innate immunity, intestinal and liver histology, and gene expression of thinlip mullet (Liza ramada) juveniles. The experimental design involved thinlip mullets initially weighing 3.5±0.13 g, distributed in a completely randomized design with 30 fish per hapa (0.5 × 0.5 × 1 m), and conducted in triplicate over 60 days. Seven experimental diets were employed, including a control (without SI and Se supplementation), a negative control (with only Se supplementation), and four treatments with varying levels of silymarin (250, 450, 650, 850 mg/kg) alongside selenium (0.5 mg/kg diet). The growth performance results highlighted significant enhancements in final body weight, weight gain, and specific growth rate, particularly in the SI 850 mg/kg + Se treatment. Survival rates, feed intake, and feed conversion ratios showed positive trends across the SI-Se supplemented groups. Biochemical profiles of serum exhibited that the control diet induced elevated concentrations of glucose, cholesterol, alanine aminotransferase, aspartate aminotransferase, and urea, while Se or SI supplementation significantly mitigated these levels, with the lowest concentrations observed in the SI-Se supplemented groups. Moreover, SI supplementation increased serum protein content. Antioxidant enzyme activities, represented by superoxide dismutase (SOD), catalase (CAT), and catalase (GPx), demonstrated notable improvements in the SI-Se fortified groups, with significantly elevated GPx activity compared to the Se-supplemented and control groups. Immune system responses, including lysozyme, bactericidal, nitro-blue tetrazolium (NBT%), and serum alternative complement pathway (ACH50) activities, were highest in the SI-Se augmented groups. SI and Se in L. ramada reduce liver pro-inflammatory gene expression (IL-1 β, hepcidin) vs. control group. Histological examinations of the intestine and liver depicted structural enhancements, especially at moderate and high levels of SI with Se supplementation. The results indicate improved intestinal villi morphology and hepatic architecture, supporting the positive influence of dietary treatments on the health of thinlip mullet juveniles. In conclusion, the combined supplementation of SI at 850 mg/kg diet and Se at 0.5 mg/kg diet positively influenced the growth, biochemical profiles, antioxidant status, immune responses, gene expression, and histological integrity of thinlip mullet juveniles, providing valuable insights for optimizing aquafeed formulations.

Decoding the genetic influence of CT60 non-coding polymorphism in CTLA-4 gene and sCTLA-4 biomarker with rheumatoid arthritis in the Indian population.

Cytoplasmic T Lymphocyte Antigen - 4 (CTLA-4) gene encodes an immunoregulatory receptor expressed on surface of activated T-cells to mediate peripheral tolerance against self-antigen. It suppresses auto-reactive T-cell proliferation either by inactivation or apoptosis of T-cells. The CTLA-4 mRNA undergoes alternative splicing to synthesize a native soluble form of CTLA-4 (sCTLA-4) protein, which lacks exon 3 that encodes for transmembrane region. As a result, sCTLA-4 circulates as a soluble serum protein and acts as an immunoregulator molecule to maintain homeostasis in the blood. Techniques coupled with quantitative Polymerase Chain Reaction (qPCR) and High-Resolution Melting Analysis (HRMA) were used to screen CTLA-4 3'Untranslated Region (UTR) CT60 (A/G) rs3087243 Single Nucleotide Polymorphism (SNP) and their association with Rheumatoid Arthritis (RA) in the Indian population. In addition, we also evaluated the concentration of sCTLA-4 serum protein in RA patients carrying rs3087243 SNP with different genotypes (A/A, G/A, and G/G). Statistical analysis of Odds Ratio (OR), Confidence Interval (C.I), and Relative Risk (RR) have shown that frequency of CTLA-4 rs3087243 SNP G/G genotype was significantly associated with RA in the Indian population (OR 1.7140; CI = 1.0765 to 2.7290; RR = 1.5434; p = 0.0232). The sCTLA-4 concentration was also significantly lower in RA patients carrying rs3087243 SNP G/G genotype than control group (p < 0.001). Co-inheritance of CTLA-4 signal peptide and 3'UTR SNPs may activate RAPP pathway. Downregulation of CTLA-4 and sCTLA-4 serum protein by rs3087243 SNP can increase the hyperactivation of T-cells, which causes RA.

Evaluation of a host-protein signature score for differentiating between bacterial and viral infections: real-life evidence from a German tertiary hospital.

A host-protein signature score, consisting of serum-concentrations of C-reactive protein, tumour necrosis factor-related apoptosis-inducing ligand, and interferon gamma-induced protein 10, was validated for distinguishing between bacterial and viral infections as an antimicrobial stewardship measure for routine clinical practice among adult patients in a German tertiary hospital. This single-centre, explorative study prospectively assessed the host-protein signature score, comparing it with serum procalcitonin (PCT) in patients with blood stream infections (BSI) and evaluating its efficacy in patients with viral infections against the standard of care (SOC) to assess the need for antibiotics due to suspected bacterial super/coinfection. Manufacturer-specified threshold scores were used to differentiate viral (< 35) and bacterial (> 65) infections. Ninety-seven patients (BSI [n = 56]; viral infections [n = 41]) were included. The score (cut-off score > 65) tended to detect BSI with higher sensitivity than did PCT (cut-off > 0.5 ng/mL) (87.5% vs. 76.6%). Three patients (5.4%) with BSI had a score < 35. One patient with BSI did not receive antibiotic treatment following SOC prior to positive blood culture results. Among patients with viral infections, 29 (70.7%) had scores > 65, indicating bacterial superinfections. Additionally, 11 patients (26.8%) had scores < 35, indicating no bacterial superinfections. In total, the antibiotic treatment discrepancy in the viral group between the SOC and a host-protein signature score guided approach was 2/41 patients (4.9%). The score tended towards a higher sensitivity in detecting BSI than that with PCT. However, its impact on reducing antibiotic use in viral infections was minor compared with that of SOC.