Serial Blood Samples Research Articles

Changes in cytokine profile as a criterion for severity prediction of skin toxicity in cancer patients receiving epidermal growth factor receptor inhibitors

BACKGROUND: Globally, colorectal cancer is the third most diagnosed cancer with an increased incidence of 1.93 million cases in 2020 according to World Health Organization. Approximately one quarter of the initial manifestations of colorectal cancer are metastatic, and 40–50% of individuals with early-stage disease eventually develop metastatic colorectal cancer (mCRC). Targeted drugs, which include epidermal growth factor receptor inhibitors (EGFRi), are a frequent choice in the therapy of metastatic colorectal cancer. Clinical observations and in vivo studies have established a significant association between the administration of EGFRi drugs and skin inflammation, particularly acute in the first 3 months. However, the role of proinflammatory cytokines in the formation of severe skin lesions has not been definitively studied. Here we present clinical evidence of the involvement of a few cytokines in the formation of the pathologic cascade of reactions during EGFR blockade on keratinocyte membranes. AIM: Evaluation of changes in cytokine profile parameters based on the MILLIPLEX Analyte MAP panel to identify predictors of the severity of unwanted skin toxicity associated with epidermal growth factor receptor inhibition. MATERIALS AND METHODS: Blood serum samples from 81 patients aged 18–80 years who were taking EGFRi for oncologic disease and had adverse dermatologic reactions of severity 2 or more were analyzed. The data were analyzed using SPSS software and R 4.3.1 programming language and tidyverse, rstatix packages. Detected changes with p 0.05 were analyzed considering subgroup analysis on the basis of selected cutaneous toxicity severity degrees based on the criteria developed by the US National Cancer Institute NCI-CTC v. 4. RESULTS: Blocking of EGF receptor inhibits the expression and release of vascular endothelial growth factor (VEGF), which is the main inducer of vascular proliferation, the consequence of which is inflammation of vascular endothelium of skin capillaries. Significant increase of IFN-γ and decrease of IFN-α2 level was found in patients with manifestations of skin toxicity of 2 and more severity degree. Also, a significant criterion of severity of the skin process was an increase in the level of TNF-α. At such dissociation there is induction of STING protein (interferon gene stimulator) and increase of TNF-β production that, in its turn, leads to increase of concentration of proinflammatory cytokines G-CSF, GM-CSF, IFN-α2, IFN-γ, IL-15, IL-17A, IL-1β, IL-3, IL-6, IL-8, IP-10, TNF-α, TGF-α, IL-9. This contributes not only to the maintenance of tissue inflammation, but also to the formation of a vicious circle leading to an increase in the severity of class-mediated inflammatory response against the background of further EGFRi administration. CONCLUSION: Determination of predictors of severity of adverse dermatologic reactions is extremely important for predicting the development of severity and further personalized tactics for correction of adverse events.

Serological monitoring of Influenza A among wild and domestic ungulates in Ukraine

The article provides a brief historical background of equine influenza, the spread of this disease worldwide, and the current epizootic situation. The results of serological monitoring by ELISA of wild and domestic ungulates from different farms and regions of Ukraine for the presence of antibodies to influenza A viruses are presented. Blood serum samples from 372 domestic horses and 32 wild ungulates were tested. Samples from animals collected in 2023 and 2024 and archival blood serum samples from 2021 were used and tested according to the manufacturer’s instructions using ELISA test systems manufactured by IDEXX, INGEZIM, and IDVet. The data obtained indicate a fairly active circulation of influenza A viruses in populations of unvaccinated domestic horses. The circulation was established not only in recent years (2023–2024, seroprevalence from 10% to 100%), but was observed earlier, as evidenced by the detection of 60.9% of positive samples in samples collected in 2021. In addition, two out of three positive samples were found in wild horses from Kherson Region, which indicates the circulation of influenza A virus among wild animals and requires further investigation. The results correlate with the worsening of the epidemiological situation regarding influenza in animals in Europe. The subsequent phase of the research is serotyping, which involves determining the presence of antibodies to specific virus subtypes by hemagglutinin

Blood Distribution of SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine in Humans.

Lipid nanoparticle mRNA vaccines are an exciting but emerging technology used in humans. There is limited understanding of the factors that influence their biodistribution and immunogenicity. Antibodies to poly(ethylene glycol) (PEG), which is on the surface of the lipid nanoparticle, are detectable in humans and boosted by human mRNA vaccination. We hypothesized that PEG-specific antibodies could increase the clearance of mRNA vaccines. To test this, we developed methods to quantify both the vaccine mRNA and ionizable lipid in frequent serial blood samples from 19 subjects receiving Moderna SPIKEVAX mRNA booster immunization. Both the vaccine mRNA and ionizable lipid peaked in blood 1-2 days post vaccination (median peak level 0.19 and 3.22 ng mL-1, respectively). The vaccine mRNA was detectable and quantifiable up to 14-15 days postvaccination in 37% of subjects. We measured the proportion of vaccine mRNA that was relatively intact in blood over time and found that the decay kinetics of the intact mRNA and ionizable lipid were identical, suggesting the intact lipid nanoparticle recirculates in blood. However, the decay rates of mRNA and ionizable lipids did not correlate with baseline levels of PEG-specific antibodies. Interestingly, the magnitude of mRNA and ionizable lipid detected in blood did correlate with the boost in the level of PEG antibodies. Furthermore, the ability of a subject's monocytes to phagocytose lipid nanoparticles was inversely related to the rise in PEG antibodies. This suggests that the circulation of mRNA lipid nanoparticles into the blood and their clearance by phagocytes influence the PEG immunogenicity of the mRNA vaccines. Overall, this work defines the pharmacokinetics of lipid nanoparticle mRNA vaccine components in human blood after intramuscular injection and the factors that influence these processes. These insights should be valuable in improving the future safety and efficacy of lipid nanoparticle mRNA vaccines and therapeutics.

On-site monitoring of L-adrenaline neurotransmitter in biological samples by chitosan oligosaccharide derived carbon dots

Carbon quantum dots (CDs) are fascinating fluorescent nanomaterial for spectrofluorimetry sensor applications, owing to the fact of its strong chemical stability, high quantum yield and high photostability. At this instance, we have developed the fluorescent sensing technique to detect the L-adrenaline (L-Adr) by nitrogen-doped carbon quantum dots as a sensing probe. The nitrogen-doped carbon dots was synthesized using chitosan oligosaccharide by hydrothermal method. The synthesized chitosan oligosaccharide derived CDs (COL-CDs) exhibits blue fluorescence under UV light and the size of the carbon quantum dots is 3.39 ± 0.08 nm calculated from HR-TEM image. The hormone called L-Adr found in the human body is crucial for controlling visceral processes. Utilizing the process of photo-induced electron transfer (PET), the previously mentioned COL-CDs have applied to sense the L-Adr. The sensing mechanism have explained clearly using Rehm-Weller equation by calculating ΔG. Tap water, blood serum, urine and adrenaline drug samples employed as real sample for the sensing L-Adr. A reagent free paper-based kit established for the purpose of on-site monitoring L-Adr. The smartphone’s colour picker software used to measure the RGB intensity from the paper-based kit.

Near-infrared photothermal lens as microfluidic analyzer for determination of phosphate in food and biological samples

In this work, photothermal lens spectrophotometer (PTLS) with crossed-beam configuration pumped by a laser diode (850 nm) was used for determination of soluble phosphorus exists mainly in the form of orthophosphate (PO43−) in nonalcoholic beverage and human blood serum samples. The determination was carried out after complexation reaction between blue molybdenum and phosphate in aqueous solution. UV–vis spectrophotometry was used by measuring absorption in the near infrared region (815 nm) for optimizing the complex formation time, concentrations of reducing agent and sulfuric acid. The UV–vis absorption measurements showed that the calibration curve was obtained in the concentration ranges of 0.5–80 mg L−1 with a linear correlation coefficient of 0.98 and a detection limit of 0.2 mg L−1. Then, PTLS at a wavelength of 850 nm after optimizing the device conditions (flow rate, excitation laser power and interrupting frequency) was used for phosphate determination. The calibration curve in the concentration range of 11–1000 µg L−1 has a correlation coefficient of 0.98 and a detection limit of 4 µg L−1. The achieved detection limit was about 50 times better than NIR absorption spectrometry using a conventional 1 cm sample cell. In PTLS with the 3 μL microfluidic cell experimental detectability amount of phosphate is 33 picogram, while in UV–vis-NIR method this amount is 1.5 µg.

Intestinal fatty acid binding protein is associated with infarct size and cardiac function in acute heart failure following myocardial infarction

BackgroundIn acute heart failure (HF), reduced cardiac output, vasoconstriction and congestion may damage the intestinal mucosa and disrupt its barrier function. This could facilitate the leakage of bacterial products into...

362 Nutrikinetic evaluation and modeling of 25-hydroxyvitamin D3 in beef cattle

Abstract The objective of this study was to evaluate serum 25-hydroxyvitamin D3 [25(OH)D3] status in beef cattle when 1) fed diets with supplemental 25(OH)D3 or calcidiol (HyD, dsm-firmenich, Plainsboro, NJ), and 2.) a single dose of calcidiol was administered to cannulated heifers on nutrikinetic evaluation and predictive modeling simulations. In experiment 1, crossbred heifer calves [n = 96, initial body weight (BW) = 222 ± 12.4 kg] were assembled from auction markets near Dickson, TN and transported ~1,069 km to Manhattan, KS. Heifers (n = 12 per pen) were stratified by BW and randomly allocated to a corn-based receiving diet with one of four dietary treatments: 1) No supplemental D3 or calcidiol (CON, n = 24), 2) 3,000 IU supplemental D3·heifer⁻¹·d⁻¹ (D3, n = 24), 3.) 0.5 mg calcidiol/h/d (Hy D Low, n = 24), or 4.) 1.0 mg calcidiol·heifer⁻¹·d⁻¹ (Hy D High, n = 24) for 60 d. Blood samples were collected from each heifer prior to transport (d -1), on arrival (d 0) and on d 14, 31, and 60 of dietary treatment period. Data were analyzed using the GLIMMIX procedure of SAS using animal as experimental unit and treatment as fixed effect. HyD High calves had greater (P < 0.001) serum 25(OH)D3 concentrations than HyD Low at d 14 and 31 (Figure 1 and 2). At d 14, 31 and 60, HyD High and HyD Low calves had greater (P < 0.001) serum 25(OH)D3 concentrations than CON or D3 treatments. In experiment 2, cannulated crossbred heifers (n = 8, initial BW = 289 ± 44.9 kg were randomly assigned to one of two treatments: 1.) 3 mg/272 kg BW calcidiol, or 2.) 5 mg/272 kg BW calcidiol in a single dose administered via rumen cannula at h 0. Serial blood samples were collected at baseline out to 70 d post-dose. Serum 25(OH)D3 concentrations were analyzed via HPLC coupled with tandem MS (dsm-firmenich, Belvidere, NJ). Predictive modeling simulations of serum 25(OH)D3 concentrations used non-parametric superposition (Certara Phoenix WinNonlin 64, St. Louis, MO) from applying non-compartmental analysis with the assumptions of linearity, independent calcidiol dose response, and the rate of absorption and the average systemic clearance were consistent for each calcidiol dosing interval. The elimination half-life (t1/2) of calcidiol was determined to be an average of 7.1 d and area under change in concentration-time curve time 0 to the last time point that measured above baseline concentration post dose (AUC0-last) averaged of 32.6 d (Table 1). Non-parametric dosing simulations using nutrikinetic parameters from experiment 2 suggest that administration of two 5 mg oral doses of calcidiol with daily feeding of 1 mg would result in a rapid and sustained increase in serum 25(OH)D3. However, simulations should be confirmed in vivo before implementation.

Sensitive electrochemical detection of methimazole based on a unique copper and exfoliated graphene oxide nanocomposite

Herein, we report the creation of a novel sensitive electrochemical sensing platform based on a copper and exfoliated graphene oxide (Cu-eGO) nanocomposite using a facile synthesis technique, which simultaneously removes the sodium ions that result from the exfoliation process to generate eGO from graphite. This novel Cu-eGO nanocomposite was characterized via SEM, EDX, Raman and XPS. The Cu-eGO/GCE exhibited much greater activity for the electrochemical oxidation of methimazole than the eGO/GCE or bare GCE. The electrochemical properties and kinetics involved in the oxidation of methimazole at the Cu-eGO were examined using voltammetry and electrochemical impedance spectroscopy (EIS). This Cu-eGO based sensing platform demonstrated high sensitivity at 1.32 μAμM−1cm−2, a low limit of detection at 0.06 μM, robust stability, and strong anti-interference against potential interferents that may exist in biological systems for the detection of methimazole. The developed electrochemical sensor was successfully employed in blood serum samples that mimicked real biological environments, showing its high applicability.

Surface-enhanced Raman spectroscopy (SERS) for the diagnosis of acute myocardial infarction (AMI) using blood serum samples.

Acute myocardial infarction (AMI) is a serious medical condition generally known as heart attack, which is caused by the decreased or completely blocked blood flow to a part of the heart muscle. It is a significant cause of both mortality and morbidity throughout the world. Cardiac troponin-I (cTnI) is an important biomarker at different stages of AMI and is one of the most specific and widely used cardiac skeletal muscle proteins. Delays in medical treatment and inaccurate diagnosis might be the main cause of death of AMI patients. To overcome the death rate of AMI patients, early diagnosis of this disease is crucial. In the current study, surface-enhanced Raman spectroscopy (SERS) is employed for the characterization and diagnosis of this disease using blood serum samples from 49 clinically confirmed acute myocardial infarction (AMI) patients and 17 healthy persons. Silver nanoparticles (AgNPs) are used as the SERS substrate for the recognition of characteristic SERS spectral features, differentiating between healthy and AMI-positive samples. The acute myocardial infarction-positive blood serum samples reveal remarkable differences in spectral intensities at 534, 697, 744, 835, 927, 941, 988, 1221, 1303, 1403, 1481, 1541, 1588 and 1694 cm-1. For the differentiation and quantitative analysis of the SERS spectra, multivariate chemometric tools (including principal component analysis (PCA) and partial least squares regression (PLSR)) are employed. A PLSR model established on the basis of differentiating the SERS spectral features is found to be helpful in the prediction of the levels of cardiac troponin-I (cTnI) in the blood serum samples with the root mean square error of calibration (RMSEC) value of 2.98 ng mL-1 and root mean square errors of prediction (RMSEP) value of 3.98 ng mL-1 for S7.

Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989

Background and aimsRNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. We aimed to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis...

Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma

AbstractEngineered cellular therapy with CD19-targeting chimeric antigen receptor T cells (CAR-Ts) has revolutionized outcomes for patients with relapsed/refractory large B-cell lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved. We analyzed serial peripheral blood samples ranging from the day of apheresis (day –28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel by integrating single-cell RNA and T-cell receptor sequencing, flow cytometry, and mass cytometry to characterize features associated with response to CAR-T. Pretreatment patient characteristics associated with response included the presence of B cells and increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC). Infusion products from responders were enriched for clonally expanded, highly activated CD8+ T cells. We expanded these observations to 99 patients from the ZUMA-1 cohort and identified a subset of patients with elevated baseline B cells, 80% of whom were complete responders. We integrated B-cell proportion ≥0.5% and ALC/AMC ≥1.2 into a 2-factor predictive model and applied this model to the ZUMA-1 cohort. Estimated progression-free survival at 1 year in patients meeting 1 or both criteria was 65% vs 31% for patients meeting neither criterion. Our results suggest that patients’ immunologic state at baseline affects the likelihood of response to CAR-T through both modulation of the T-cell apheresis product composition and promoting a more favorable circulating immune compartment before therapy. These baseline immunologic features, measured readily in the clinical setting before CAR-T, can be applied to predict response to therapy.

SEROLOGICAL INCIDENCE OF CONTAGIOUS PLEUROPNEUMONIA OF GOATS IN TAJIKISTAN

The article presents data on serological monitoring of contagious pleuropneumonia of goats in goat farms in Tajikistan. As a result of selective serological studies using enzyme immunoassay (ELISA test), it was found that contagious pleuropneumonia of goats has a high incidence in farms of the Republic of Tajikistan and causes significant economic damage to goat farms.Enzyme immunoassay of 159 samples of blood serum of goats of local breed from 9 goat farms in 7 districts of the country seropositivity was found in 54 animal heads, which was 34%. The most widespread PDAs were noted in the goat farms of the Rudaki, A. Jami and Rasht districts, respectively 80.45 and 40%.

Optimization and adaptation of amperometric biosensor based on lactate oxidase for measuring lactate concentration in blood serum samples

Optimization and adaptation of amperometric biosensor based on lactate oxidase for measuring lactate concentration in blood serum samples

CORRELATION BETWEEN BMI AND GONADOTROPIN HORMONES IN THE FEMALE GENDER

Introduction: The pituitary gland affects growth and development. Its main function is in the activity of sexual/reproductive hormones and in the functioning of the glands (thyroid gland, adrenal glands and gonads). Gonadotropin hormones (gonadostimulins) are so named because they stimulate the function of the gonads - male and female sex glands (testicles and ovaries) in which sex cells - sperm and egg cells are created. Overweight is a state of metabolic disorders where excess body fat accumulates to the extent that it can negatively affect human health. Obesity as a BMI factor is related to the functioning of the thyroid gland with its hormones and the pituitary gland with gonadotropin hormones. Purpose of the study: This paper aims to present the correlation between BMI and gonadotropin hormones in reproductive and postmenopausal women. The aim of the paper will also consist in the status of gonadotropin hormones and the functional state of these hormones by comparing them with metabolic disorders such as BMI, obesity and the synthesis of follicle stimulating hormone and gonadotropin hormone. Material and method: A total of 20 patients will be included in the research, divided according to age group into two categories. The first group will include patients aged 10-40 years, the second group patients over 41 years old. Blood (serum) samples will be taken from patients for analyzing gonadotropin hormones: FSH, LH, PRL and thyroid hormones: TSH, FT4, FT3. They will be analyzed with the modern automatic fluorescent enzyme immunoassay method (Vidas-Biomerie). The BMI of the body will be measured with a metric formula where the weight of the patient (in kg) divided by the height of the patient (in m2) set to the square power will give us the measure of body index-BMI (%). SPSS – Software package version 20.0 Numerical series were analyzed using central tendency measures (average, median, minimum values, maximum values), as well as distribution measures (standard deviation); To determine the regularity of the frequency distribution of the examined variables, the Shapiro-Wilk W Test was used; Non-parametric tests for two independent parameters were used to test the significance and difference between some numerical parameters with irregular frequency distribution (Mann Whitney U test); To determine statistical significance, a two-way analysis was used with a significance level (means) of p<0.05. Results: The results of the research will give a real insight into the data of gonadotropic hormones FSH, LH, PRL and thyroid hormones TSH, FT4, FT3 of the female sex in the Tetova region. The results of the research will also provide information about the correlation of BMI and gonadotropin and thyroid hormones. Conclusion: From the analyzes performed on patients of different age groups we come to the conclusion that: • Gonadotropin hormonal disorders can lead to the phenomenon of metabolic diseases such as BMI. • These disorders can have consequences such as: polycystic ovary diseases in women, Hashimoto's genetic syndrome, Graves, infertility in women, etc.

Pharmacokinetics of olverembatinib (HQP1351) in the presence of a strong CYP3A4 inhibitor (itraconazole) or inducer (rifampin) in healthy volunteers.

Olverembatinib (HQP1351) is a BCR-ABL1 tyrosine kinase inhibitor with promising clinical activity. It is approved in China for the treatment of patients with chronic myeloid leukemia harboring drug-resistant mutations, such as T315I. Invitro studies suggested that metabolism of olverembatinib is primarily mediated by cytochrome P450 (CYP3A4). The effects of CYP3A4 inhibition and induction on the pharmacokinetics of olverembatinib were evaluated in an open-label, 2-part, fixed-sequence study in healthy volunteers. In Part 1 of this study, 16 participants received a single oral dose of olverembatinib (20 mg) and the oral CYP3A4 inhibitor itraconazole (200 mg). In Part 2, 16 participants received a single oral dose of olverembatinib (40 mg) and the oral CYP3A4 inducer rifampin (600 mg). To measure pharmacokinetic parameters, serial blood samples were collected after administration of olverembatinib alone and combined with itraconazole or rifampin. Coadministration of olverembatinib with itraconazole increased the peak plasma concentration of olverembatinib, its area under the time-concentration curve (AUC)0-last, and AUC0-inf by 75.63%, 147.06%, and 158.66%, respectively. Coadministration with rifampin decreased these same variables by 61.27%, 74.21%, and 75.19%, respectively. These results confirm that olverembatinib is primarily metabolized by CYP3A4 in humans, suggesting that caution should be exercised with concurrent use of olverembatinib and strong CYP3A4 inhibitors or inducers.

The Physical Home Food Environment in Relation to Children’s Diet Quality and Cardiometabolic Health

BackgroundHome food availability has been identified as an important influence on dietary intake. Less is known about the relationship between the physical home food environment (HFE) and factors of cardiometabolic health in children. ObjectiveThe purpose of this study was to explore the relationship between the physical HFE and diet quality and factors of cardiometabolic health (eg, weight and blood biomarkers). DesignThis was a cross-sectional secondary analysis with 1 or more children per household. Participants/settingThis study included 44 children aged 6 to 12 years from 29 households in the Newark, DE area between August 2020 and August 2021. Main outcome measuresThe Home Food Inventory provides an obesogenic score (ie, score indicative of the presence of energy-dense foods) for the overall HFE and HFE subcategories scores; body mass index z-scores were calculated using measured height and weight; diet quality was measured using the Healthy Eating Index 2020 (HEI-2020) total scores; and cardiometabolic biomarkers were obtained from serum blood samples. Statistical analyses performedUnadjusted and adjusted linear mixed model regressions were used to test the association between the physical HFE and each of the outcome variables: body mass index z scores, HEI-2020 total scores, and cardiometabolic biomarkers. HFE subcategories (eg, fruits and vegetables) were also examined with each outcome using linear mixed model regression. ResultsMean ± SD age of the children was 9.5 ± 1.9 years, 61.4% were female, 59.1% identified as White, and 90.9% were non-Hispanic. Obesogenic score was significantly associated with body mass index z scores (β = .03, P = .029), but not HEI-2020 total scores or cardiometabolic biomarkers. As HFE fruits and vegetables subcategory increased, HEI-2020 total scores significantly increased (β = .73, P = .005) and total cholesterol (β = –1.54, P = .014) and low-density lipoprotein cholesterol levels (β = –1.31, P = .010) significantly decreased. Increased availability of sweet and salty snack food and availability of sugar-sweetened beverages was associated with increased fasting blood glucose (β = 0.65, P = .033) and insulin levels (β = 5.60, P = .035) respectively. ConclusionsThere is evidence of a relationship between the subcategories of the physical HFE and cardiometabolic factors. Future interventions are needed to understand whether altering the overall HFE or specific subcategories within the HFE can improve cardiometabolic health.

Investigation of the effects of IL-13 and IL-22 cytokine levels on disease activity, prognosis, and treatment response in multiple sclerosis patients treated with fingolimod and glatiramer acetate

Background: Multiple Sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease. In this study, we investigated serum protein levels of Interleukin-13 (IL-13) and Interleukin-22 (IL-22) cytokines. These cytokines play an important role in the generation and regulation of the inflammatory response, which is the pathogenesis of MS, and are potential biomarkers for monitoring therapeutic response. cytokines may play a role in the development of MS lesions. Methods: The study included 66 MS patients and 22 healthy individuals. IL-13 and IL-22 cytokine protein levels were measured by ELISA from peripheral blood serum samples collected from the participants. Patient demographics and treatment history data were also collected. Results: IL-13 and IL-22 parameters were lower in MS patients compared to the control group. There was a significant difference between the patient and control groups in terms of IL-13 (p<0.001). Although the mean IL-22 level of the control group was higher than the patient group, the difference did not reach a significant level (p: 0.257). Conclusion: The results of the study suggest that IL-13 and IL-22 cytokines play an important role in the pathogenesis of MS and are affected by fingolimod and glatiramer acetate treatment.

The role of cytokines in acute and chronic postsurgical pain after major musculoskeletal surgeries in a quaternary pediatric center

Study ObjectiveTo determine if baseline cytokines/chemokines and their changes over postoperative days 0–2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery. DesignProspective, observational, longitudinal nested study. SettingUniversity-affiliated quaternary children’s hospital. PatientsSubjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure. MeasurementsDemographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and up to two weeks after surgery, using Luminex bead arrays. After data preparation, relationships between pre- and post-surgical cytokine concentrations with acute (% time in moderate-severe pain over POD0-2) and chronic (pain score > 3/10 beyond 3 months post-surgery) post-surgical pain were analyzed using univariable and multivariable regression analyses with adjustment for covariates and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes. Main ResultsAnalyses included 3,164 repeated measures of 16 cytokines/chemokines from 112 subjects (median age 15.3, IQR 13.5–17.0, 54.5 % female, 59.8 % pectus). Acute postsurgical pain was associated with higher baseline concentrations of GM-CSF (β = 0.95, SE 0.31; p = 0.003), IL-1β (β = 0.84, SE 0.36; p = 0.02), IL-2 (β = 0.78, SE 0.34; p = 0.03), and IL-12 p70 (β = 0.88, SE 0.40; p = 0.03) and longitudinal postoperative elevations in GM-CSF (β = 1.38, SE 0.57; p = 0.03), IFNγ (β = 1.36, SE 0.6; p = 0.03), IL-1β (β = 1.25, SE 0.59; p = 0.03), IL-7 (β = 1.65, SE 0.7; p = 0.02), and IL-12 p70 (β = 1.17, SE 0.58; p = 0.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (β = -0.39, SE 0.17; p = 0.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (β = -0.57, SE 0.26; p = 0.03), IL-8 (β = -0.68, SE 0.24; p = 0.006), and IL-13 (β = -0.48, SE 0.22; p = 0.03). Covariates female (vs. male) sex and surgery type (pectus surgery vs. spine) were associated with higher odds for CPSP in baseline adjusted cytokine-CPSP association models for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNFα, and IL-8, IL-10, respectively. ConclusionWe identified pro-inflammatory cytokine profiles associated with higher risk of acute postoperative pain. Interestingly, pleiotropic cytokine IL-6, chemokine IL-8 (which promotes neutrophil infiltration and monocyte differentiation), and monocyte-released anti-inflammatory cytokine IL-13, were associated with lower CPSP risk. Our results suggest heterogenous outcomes of cytokine/chemokine signaling that can both promote and protect against post-surgical pain. These may serve as predictive and prognostic biomarkers of pain outcomes following surgery.

Study on interaction with high-abundant blood proteins and identification of low-abundant proteins to 5-phenyl-1-(p-tolyl)-1 H-1,2,3-triazole by serum proteomics

In this study, a comprehensive investigation was undertaken to elucidate a simple triazole compound, 5-phenyl-1-(p-tolyl)-1 H-1,2,3-triazole (PPTT), its interactions with high-abundant proteins and identification of low-abundant proteins by serum proteomics. Employing a combination of spectroscopic techniques and computational chemistry, the interactions between PPTT and three high-abundance blood globular proteins, namely human serum albumin (HSA), human immunoglobulin G (HIgG), and hemoglobin (BHb), were explored, thereby ascertaining their binding constants and thermodynamic parameters at the molecular level. Subsequently, based on the differential proteomics, utilizing two-dimensional gel electrophoresis (2-DE) in conjunction with matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS), the research team isolated and identified differentially expressed low-abundance proteins in human blood serum samples following exposure to PPTT. The results showed that there were twenty highly expressed proteins identified from blood serum samples intervened by PPTT. Combining bioinformatics techniques, these proteins were classified, providing preliminary insights like preproprotein or precursors inhibiting the activity of elastase, defending and regulating the immune system, carrying lipid, and other functions into their biological functionalities. One of the differential proteins, apolipoprotein A-1 (ApoA-1) protein, was selected as a possible target to explore the mechanism of action of PPTT intervention on the related signaling pathways involved in human hepatocellular carcinomas(Hep G2) cells. These research findings offer scientifically sound guidance for further in-depth exploration, development, and application of the 1,2,3-triazole compound.

In Vivo Activity of Intestinal P-Glycoprotein and Hepatic Organic Anion Transporters Polypeptide in Pregnancy and Postpartum.

This study investigates the influence of pregnancy on the in vivo activity of the intestinal P-glycoprotein (P-gp) and hepatic organic anion transporters polypeptide (OATP/BCRP) using, respectively, fexofenadine and rosuvastatin as probe drugs. Eleven healthy participants were investigated during the third trimester of pregnancy (Phase 1, 28 to 38 weeks of gestation) and in the postpartum period (Phase 2, 8 to 12 weeks postpartum). In both phases, after administration of a single oral dose of fexofenadine (60 mg) and rosuvastatin (5 mg), serial blood samples were collected for up to 24 h. Rosuvastatin and fexofenadine in plasma were analyzed by LC-MS/MS using previously validated methods. The pharmacokinetic parameters of fexofenadine and rosuvastatin (Phoenix WinNonLin software) with normal distribution (Shapiro-Wilk test) are presented as geometric mean and 90% confidence interval. Phases 1 and 2 were compared using the t test (P < .05). Fexofexadine AUC0-24 values do not differ (P-value: .0715) between Phase 1 (641.9ng h/mL [500.6-823.1]) and Phase 2 (823.8ng h/mL [641.5-1057.6]) showing that pregnancy (third trimester) does not alter intestinal P-gp activity. However, rosuvastatin AUC0-24 values are higher (P-value: .00005) in Phase 1 (18.7 ng h/mL [13.3-26.4]) when compared to Phase 2 (9.5 ng h/mL [6.7-13.4]), suggesting inhibition of OATP1B1/OATP1B3 transporters. In conclusion, pregnancy assessed during the third trimester does not alter the intestinal P-gp activity but reduces the activity of hepatic OATP1B1/OATP1B3 transporters. Therefore, adjustments in dosage regimens may be necessary for drugs with low therapeutic index, substrates of the OATP1B1/OATP1B3 transporters, administered during the third trimester of pregnancy.