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Background: Chronic hand eczema (CHE) is a highly prevalent, heterogeneous, skin disease that encompasses different aetiological and clinical subtypes. Severe CHE without atopic dermatitis has been associated with systemic inflammation; yet it remains unknown if specific CHE subtypes leave distinct, systemic, molecular signatures. Objectives: To characterize the inflammatory plasma signature of different aetiological and clinical CHE subtypes. Methods: We assessed expression levels of 266 inflammatory and cardiovascular disease risk plasma proteins as well as filaggrin gene mutation status in 51 well‐characterized CHE patients without concomitant atopic dermatitis and 40 healthy controls. Plasma protein expression was compared between aetiological and clinical CHE subgroups and controls both overall and according to clinical CHE severity. Correlation analyses for biomarkers, clinical and self‐reported variables were performed. Results: Very severe, chronic allergic contact dermatitis (ACD) on the hands was associated with a mixed Type 1/Type 2 systemic immune activation as compared with controls. Circulating levels of Type 1/Type 2 inflammatory biomarkers correlated positively with clinical disease severity among CHE patients with ACD. No biomarkers were found, that could discriminate between aetiological subtypes, for example, between ACD and irritant contact dermatitis. Hyperkeratotic CHE showed a distinct, non‐atopic dermatitis‐like, systemic footprint with upregulation of markers associated with Type 1 inflammation and tumour necrosis factor alpha, but not Type 2 inflammation. Increased levels of CCL19 and CXCL9/10 could discriminate hyperkeratotic CHE from both vesicular and chronic fissured CHE, whereas no difference was found between the latter two subtypes. Conclusion: Profiling of systemic biomarkers showed potential for identifying certain CHE subtypes. Peripheral blood levels of inflammatory biomarkers were associated and correlated with the clinical disease severity of chronic ACD on the hands, underlining that this is a systemic disease. We question whether hyperkeratotic CHE should be classified as eczema. [ABSTRACT FROM AUTHOR]

Accounting for variability in plasma protein binding of drugs is an essential input to physiologically-based pharmacokinetic (PBPK) models of special populations. Prediction of fraction unbound in plasma (fu) in such populations typically considers changes in plasma protein concentration while assuming that the binding affinity remains unchanged. A good correlation between predicted vs observed fu data reported for various drugs in a given special population is often used as a justification for such predictive methods. However, none of these analyses evaluated the prediction of the fold-change in fu in special populations relative to the reference population. This would be a more appropriate assessment of the predictivity, analogous to drug-drug interactions. In this study, predictive performance of the single protein binding model was assessed by predicting fu for alpha-1-acid glycoprotein and albumin bound drugs in hepatic impairment, renal impairment, paediatric, elderly, patients with inflammatory disease, and in different ethnic groups for a dataset of >200 drugs. For albumin models, the concordance correlation coefficients for predicted fu were >0.90 for 16 out of 17 populations with sub-groups, indicating strong agreement between predicted and observed values. In contrast, concordance correlation coefficients for predicted fold-change in fu for the same dataset were <0.38 for all populations and sub-groups. Trends were similar for alpha-1-acid glycoprotein models. Accordingly, the predictions of fu solely based on changes in protein concentrations in plasma cannot explain the observed values in some special populations. We recommend further consideration of the impact of changes in special populations to endogenous substances that competitively bind to plasma proteins, and changes in albumin structure due to posttranslational modifications. PBPK models of special populations for highly bound drugs should preferably use measured fu data to ensure reliable prediction of drug exposure or compare predicted unbound drug exposure between populations knowing that these will not be sensitive to changes in fu. [ABSTRACT FROM AUTHOR]

Background/Objectives: Clinical responses to naldemedine vary between individuals with advanced cancer. This is a prospective, single‐center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses. Methods: Forty‐eight patients being treated with naldemedine for opioid‐induced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed. Results: Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous CYP3A5*3 had a higher plasma concentration of naldemedine than those with the *1 allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4β‐hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin‐6 (IL‐6) and acute‐phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, CYP3A5*3/*3, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements. Conclusion: Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL‐6 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this preliminary investigation into the pathogenesis of pre‐eclampsia was to screen the differential proteins in the serum of pregnant women with normal pregnancy and early‐onset pre‐eclampsia using isobaric tags for relative and absolute quantitation (iTRAQ), so as to identify serum biomarkers for the early diagnosis of pre‐eclampsia. Methods: We examined the peripheral serum of 58 normal pregnant women and 42 pregnant women with early‐onset pre‐eclampsia using iTRAQ; the differentially expressed proteins were screened for bioinformatics analysis; and the expression of candidate proteins human leukocyte antigen‐1 (HLA‐1) and β2‐microglobulin (β2M) in placental tissues was detected using western blot. Results: We identified a total of 63 differential proteins in the serum of patients from the normal control group and the pre‐eclampsia group, and this included 24 up‐regulated proteins and 39 down‐regulated proteins. The western blot results of placental tissue showed reduced HLA‐1 expression (1.12 ± 0.23) in the placenta in the pre‐eclampsia group as compared with the normal control group (1.34 ± 0.22). Consistent with the results observed in the serum, β2M in the placenta in the pre‐eclampsia group was significantly elevated (1.05 ± 0.47) in comparison with the normal group (0.75 ± 0.33) (P < 0.05). Conclusion: In this study, we found that iTRAQ technology was useful for identifying differentially expressed proteins in the peripheral serum of pregnant women with pre‐eclampsia, and that HLA‐1 and β2M, which may be involved in the occurrence of pre‐eclampsia, show promise as predictive markers of pre‐eclampsia. Synopsis: This study used iTRAQ to identify differential proteins in pregnant women with pre‐eclampsia, indicating HLA‐1 and β2M as potential predictive markers for early diagnosis. [ABSTRACT FROM AUTHOR]

This study aimed to explore the inhibitory effect of pyrogallol on AGE formation in the bovine serum albumin (BSA)/glucose system for 21 days at 37 °C. The AGEs formation was measured in terms of Amadori products, total AGEs, argpyrimidine, and pentosidine. Molecular docking was used to investigate the interaction between pyrogallol and BSA. According to the results, in the presence of pyrogallol, the formation of pentosidine and argpyrimidine AGEs decreased. The molecular interaction studies demonstrated that pyrogallol has a high affinity towards arginine residues of albumin. Finally, results proved pyrogallol is a vigorous antiglycation compound and fruitful for AGE inhibition. [ABSTRACT FROM AUTHOR]

Copper is an indispensable trace element in metabolism. This study aimed to investigate the relationship between copper and reproductive health, and possibly provide new insights for diagnosis and treatment. This study was based on data extracted from the NHANES database (2013–2014 and 2015–2016). The t-test, ANOVA, Chi-square test, multiple linear regression, and restricted cubic spline analysis were used. Serum copper levels were significantly higher in women with gestational diabetes than in those without gestational diabetes (P = 0.0150). Women with higher copper levels and smoking habits tended to deliver overweight babies (P = 0.028). Women with diabetes had higher serum copper and were prone to deliver overweight babies (P = 0.024). Serum copper levels showed a positive relationship with sex hormone-binding globulin (SHBG) levels (P < 0.0001). In this study, serum copper levels were found to be associated with reproductive health in women. Further studies are required to draw causal inferences. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the interactive effect of a glycine equivalent (Glyequi) and standardized ileal digestible threonine (SID Thr) levels in low crude protein diets on performance, blood biochemistry, pectoral muscular creatine content and oxidative stability of meat in broiler chickens from 21 to 42 days. Methods: A total of 1,500, twenty-one-day-old Cobb-Vantress male broiler chickens were distributed in a completely randomized 5×3 factorial arrangement of Glyequi×SID Thr with five replicates of 20 birds each. Fifteen dietary treatments of 16.5% CP were formulated to contain five levels of total Glyequi (1.16%, 1.26%, 1.36%, 1.46%, and 1.56%) and three levels of SID Thr (0.58%; 0.68% and 0.78%). Results: Interaction effects (p<0.05) of Glyequi and SID Thr levels were observed for weight gain, carcass yield, pectoral muscular creatine content and serum uric acid. Higher levels of Glyequi increased (p = 0.040) weight gain in 0.58% and 0.68% SID Thr diets compare to the 0.78% SID Thr diet. The SID Thr level at 0.68% improved (p = 0.040) feed conversion compared to other SID Thr diets. Levels of Glyequi equal to or above 1.26% in diets with 0.78% SID Thr resulted in birds with higher (p = 0.033) pectoral muscular creatine content. The breast meat yield observed in the 0.68% SID Thr diet was higher (p = 0.05) compared to the 0.58% SID Thr diet. There was a quadratic effect of Glyequi levels for pectoral pectoral muscular creatine content (p = 0.008), breast meat yield (p = 0.030), and serum total protein concentrations (p = 0.040), and the optimal levels were estimated to be 1.47%, 1.35%, and 1.40% Glyequi, respectively. The lowest (p = 0.050) concentration of malondialdehyde in the breast meat was found in 0.68% SID Thr diets at 1.36% Glyequi. Conclusion: The minimum dietary level of Glyequi needed to improve performance in low crude protein diets is 1.26% with adequate SID Thr levels for broiler chickens. [ABSTRACT FROM AUTHOR]

Background: Upon infection activated plasma cells produce large quantities of antibodies which can lead to the emergence of a monoclonal component (MC), detectable by serum protein electrophoresis (SPEP). This study aims to investigate any correlation between SARS‐CoV‐2 infection and MC development and, if identified, whether it persists during follow‐up. Methods: SPEPs of 786 patients admitted to hospitals between March 01 2020 and March 31 2022 were evaluated. Positive (SARS‐CoV‐2+) and negative (SARS‐CoV‐2−) patients to nasopharyngeal swab for SARS‐CoV‐2 by RT‐PCR were included. The persistence/new occurrence of MC was investigated for all patients during follow‐up. Patient groups were compared by chi‐square analysis. Results: MC was identified in 12% of all patients admitted to hospital, of which 28.7% were SARS‐CoV‐2+. The most common immunoglobulin isotype in both groups was IgG‐k. There was no correlation between MC development and SARS‐CoV‐2 infection (p = 0.173). Furthermore, the risk of MC persistence in SARS‐CoV‐2‐negative patients was revealed to be higher than in the SARS‐CoV‐2+ at follow‐up (HR = 0.591, p = 0.05). Conclusions: Our study suggests that the detection of MC during SARS‐CoV‐2 infection is most likely due to the hyperstimulation of the humoral immune system, as also occurs in other viral infections. [ABSTRACT FROM AUTHOR]

Background: This study investigated the role of the thoracic skeletal muscle mass as a marker of sarcopenia on postoperative mortality in pleural empyema. Methods: All consecutive patients (n = 103) undergoing surgery for pleural empyema in a single tertiary referral center between January 2020 and December 2022 were eligible for this study. Thoracic skeletal muscle mass index (TSMI) was determined from preoperative computed tomography scans. The impact of TSMI and other potential risk factors on postoperative in‐hospital mortality was retrospectively analyzed. Results: A total of 97 patients were included in this study. The in‐hospital mortality rate was 13.4%. In univariable analysis, low values for preoperative TSMI (p = 0.020), low preoperative levels of thrombocytes (p = 0.027) and total serum protein (p = 0.046) and higher preoperative American Society of Anesthesiologists (ASA) category (p = 0.007) were statistically significant risk factors for mortality. In multivariable analysis, only TSMI (p = 0.038, OR 0.933, 95% CI: 0.875–0.996) and low thrombocytes (p = 0.031, OR 0.944, 95% CI: 0.988–0.999) remained independent prognostic factors for mortality. Conclusions: TSMI was a significant prognostic risk factor for postoperative mortality in patients with pleural empyema. TSMI may be suitable for risk stratification in this disease with high morbidity and mortality, which may have further implications for the selection of the best treatment strategy. [ABSTRACT FROM AUTHOR]

Background: While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework. Methods: Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications. Results: Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR. Conclusion: Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a complicated condition involving multiple metabolic and immunologic pathophysiological processes that can occur with the hallmark pathologies of amyloid-β, tau, and neurodegeneration. Metformin, an anti-diabetes drug, targets several of these disease processes in in vitro and animal studies. However, the effects of metformin on human cerebrospinal fluid (CSF) and plasma proteins as potential biomarkers of treatment remain unexplored. Objective: Using proteomics data from a metformin clinical trial, identify the impact of metformin on plasma and CSF proteins. Methods: We analyzed plasma and CSF proteomics data collected previously (ClinicalTrials.gov identifier: NCT01965756, conducted between 2013 and 2015), and conduced bioinformatics analyses to compare the plasma and CSF protein levels after 8 weeks of metformin or placebo use to their baseline levels in 20 non-diabetic patients with mild cognitive impairment (MCI) and positive AD biomarkers participants. Results: 50 proteins were significantly (unadjusted p < 0.05) altered in plasma and 26 in CSF after 8 weeks of metformin use, with 7 proteins in common (AZU1, CASP-3, CCL11, CCL20, IL32, PRTN3, and REG1A). The correlation between changes in plasma and CSF levels of these 7 proteins after metformin use relative to baseline levels was high (r = 0.98). The proteins also demonstrated temporal stability. Conclusions: Our pilot study is the first to investigate the effect of metformin on plasma and CSF proteins in non-diabetic patients with MCI and positive AD biomarkers and identifies several candidate plasma biomarkers for future clinical trials after confirmatory studies. [ABSTRACT FROM AUTHOR]

Simple Summary: In order to ensure the profitability of the broiler industry, it is essential to maintain optimal performance, especially under undesirable environmental conditions. Elevation in environmental temperatures and its subsequent negative impacts on broilers' physiological and metabolic homeostasis deleteriously affect production performance. Early adaptation is an effective strategy for ensuring sustainable broiler production. We investigated three early feed withdrawal (FWD) regimes for 24 h, either continuous or equally distributed over two or three days, as potential thermal stress-mitigating strategies. The results demonstrated a positive adjustment in metabolic hormones and biochemical metabolite markers in addition to an elevation in antioxidant enzyme activity and immune response in the FWD groups. Finally, we established that the investigated FWD strategies can promote broiler thermotolerance adaptation, reflected in the significant enhancement in broiler production performance, immunomodulation response, and recovery of the antioxidant balance. Heat stress is one of the stressors that negatively affect broiler chickens, leading to a reduction in production efficiency and profitability. This reduction affects the economy in general, especially in hot and semi-hot countries. Therefore, improving heat tolerance of broiler chicks is a key to sustained peak performance, especially under adverse environmental heat stress conditions. The present study investigated three early feed withdrawal regimes (FWD) as a potential mitigation for thermal stress exposure. A total of 240 unsexed one-day-old Cobb-500 chicks were randomly recruited to one of four experimental groups using a completely randomized design (10 birds × 6 replicates). The experimental groups included the control group with no feed withdrawal (control), while the other three groups were subjected to early feed withdrawal for either 24 h on the 5th day of age (FWD-24), 12 h on the 3rd and 5th day of age (FWD-12), or 8 h on the 3rd, 4th, and 5th day of age (FWD-8), respectively. Production performance was monitored throughout the experiment. Meanwhile, blood and liver samples were taken at the end of the experimental period to evaluate major physiological dynamic changes. Our findings demonstrated that under chronic heat stress conditions, FWD treatments significantly improved broilers' production performance and enhanced several physiological parameters compared with the control. Serum levels of thyroid hormones were elevated, whereas leptin hormone was decreased in FWD groups compared with the control. Moreover, serum total protein, globulin, and hemoglobin levels were higher, while total cholesterol and uric acid were lower in the FWD groups. Furthermore, FWD groups showed significantly higher antioxidant marker activity with a significantly lower lipid peroxidation level. Immunoglobulin levels, lysozyme, complement factor C3, and liver heat shock protein 70 (HSP70) concentration were also elevated in FWD compared with the control. Also, serum interleukin-1β (IL-1β) and interferon-gamma (IFN-γ) significantly increased with FWD. Based on our findings, early feed withdrawal can be applied as a promising non-invasive nutritional strategy for broilers reared under chronic heat stress conditions. Such a strategy promotes the alleviation of the deleterious effects of heat stress on broiler performance, immunity, and redox status, owing to the onset of physiological adaptation and the development of thermotolerance ability. [ABSTRACT FROM AUTHOR]

Viral strains, age, and host factors are associated with variable immune responses against SARS-CoV-2 and disease severity. Puerto Ricans have a genetic mixture of races: European, African, and Native American. We hypothesized that unique host proteins/pathways are associated with COVID-19 disease severity in Puerto Rico. Following IRB approval, a total of 95 unvaccinated men and women aged 21–71 years old were recruited in Puerto Rico from 2020–2021. Plasma samples were collected from COVID-19-positive subjects (n = 39) and COVID-19-negative individuals (n = 56) during acute disease. COVID-19-positive individuals were stratified based on symptomatology as follows: mild (n = 18), moderate (n = 13), and severe (n = 8). Quantitative proteomics was performed in plasma samples using tandem mass tag (TMT) labeling. Labeled peptides were subjected to LC/MS/MS and analyzed by Proteome Discoverer (version 2.5), Limma software (version 3.41.15), and Ingenuity Pathways Analysis (IPA, version 22.0.2). Cytokines were quantified using a human cytokine array. Proteomics analyses of severely affected COVID-19-positive individuals revealed 58 differentially expressed proteins. Cadherin-13, which participates in synaptogenesis, was downregulated in severe patients and validated by ELISA. Cytokine immunoassay showed that TNF-α levels decreased with disease severity. This study uncovers potential host predictors of COVID-19 severity and new avenues for treatment in Puerto Ricans. [ABSTRACT FROM AUTHOR]

Previous omics research in patients with complex congenital heart disease and single-ventricle circulation (irrespective of the stage of palliative repair) revealed alterations in cardiac and systemic metabolism, inter alia abnormalities in energy metabolism, and inflammation, oxidative stress or endothelial dysfunction. We employed an affinity-proteomics approach focused on cell surface markers, cytokines, and chemokines in the serum of 20 adult Fontan patients with a good functioning systemic left ventricle, and we 20 matched controls to reveal any specific processes on a cellular level. Analysis of 349 proteins revealed 4 altered protein levels related to chronic inflammation, with elevated levels of syndecan-1 and glycophorin-A, as well as decreased levels of leukemia inhibitory factor and nerve growth factor-ß in Fontan patients compared to controls. All in all, this means that Fontan circulation carries specific physiological and metabolic instabilities, including chronic inflammation, oxidative stress imbalance, and consequently, possible damage to cell structure and alterations in translational pathways. A combination of proteomics-based biomarkers and the traditional biomarkers (uric acid, γGT, and cholesterol) performed best in classification (patient vs. control). A metabolism- and signaling-based approach may be helpful for a better understanding of Fontan (patho-)physiology. Syndecan-1, glycophorin-A, leukemia inhibitory factor, and nerve growth factor-ß, especially in combination with uric acid, γGT, and cholesterol, might be interesting candidate parameters to complement traditional diagnostic imaging tools and the determination of traditional biomarkers, yielding a better understanding of the development of comorbidities in Fontan patients, and they may play a future role in the identification of targets to mitigate inflammation and comorbidities in Fontan patients. [ABSTRACT FROM AUTHOR]

A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids, i.e., allocryptopine (ACP) and protopine (PP), was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA's drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/quinaldine red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins' structures remained largely unchanged, suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural product–protein interactions and the future design of isoquinoline alkaloid-based therapeutics. [ABSTRACT FROM AUTHOR]

Knowledge of the composition of proteins that interact with plasma DNA will provide a better understanding of the homeostasis of circulating nucleic acids and the various modes of interaction with target cells, which may be useful in the development of gene targeted therapy approaches. The goal of the present study is to shed light on the composition and architecture of histone-containing nucleoprotein complexes (NPCs) from the blood plasma of healthy females (HFs) and breast cancer patients (BCPs) and to explore the relationship of proteins with crucial steps of tumor progression: epithelial–mesenchymal transition (EMT), cell proliferation, invasion, cell migration, stimulation of angiogenesis, and immune response. MALDI-TOF mass spectrometric analysis of NPCs isolated from blood samples using affine chromatography was performed. Bioinformatics analysis showed that the shares of DNA-binding proteins in the compositions of NPCs in normal and cancer patients are comparable and amount to 40% and 33%, respectively; in total, we identified 38 types of DNA-binding motifs. Functional enrichment analysis using FunRich 3.13 showed that, in BCP blood, the share of DNA-binding proteins involved in nucleic acid metabolism increased, while the proportion of proteins involved in intercellular communication and signal transduction decreased. The representation of NPC passenger proteins in breast cancer also changes: the proportion of proteins involved in transport increases and the share of proteins involved in energy biological pathways decreases. Moreover, in the HF blood, proteins involved in the processes of apoptosis were more represented in the composition of NPCs and in the BCP blood—in the processes of active secretion. For the first time, bioinformatics approaches were used to visualize the architecture of circulating NPCs in the blood and to show that breast cancer has an increased representation of passenger proteins involved in EMT, cell proliferation, invasion, cell migration, and immune response. Using breast cancer protein data from the Human Protein Atlas (HPA) and DEPC, we found that 86% of NPC proteins in the blood of BCPs were not previously annotated in these databases. The obtained data may indirectly indicate directed protein sorting in NPCs, which, along with extracellular vesicles, can not only be diagnostically significant molecules for liquid biopsy, but can also carry out the directed transfer of genetic material from donor cells to recipient cells. [ABSTRACT FROM AUTHOR]

Background: Determination of the functional liver mass is important in a variety of clinical settings including liver surgery and transplantation. [99mTc]Tc-diethylenetriamine-pentaacetic acid galactosyl human serum albumin (99mTc-GSA) is a radiotracer targeting the asialoglycoprotein receptor (ASGR) and is routinely used in Japan for this purpose. Here we describe the development and evaluation of [68Ga]Ga-NODAGA-TriGalactan a low molecular weight PET-tracer targeting this structure. Results: For synthesis TRIS as branching unit and NODAGA as chelator for labelling with [68Ga]Ga are included. Three galactose moieties are conjugated via a click chemistry approach resulting in the desired labelling precursor.68Ga-labelling could be accomplished in high radiochemical yield and purity. [68Ga]Ga-NODAGA-TriGalactan is very hydrophilic and revealed high plasma stability and low plasma protein binding. Fluorescence imaging showed binding on ASGR-positive organoids and the IC50-value was in the nanomolar range. Most importantly, both biodistribution as well as animal imaging studies using normal mice demonstrated high liver uptake with rapid elimination from all other organs leading to even higher liver-to-background ratios as found for 99mTc-GSA. Conclusion: [68Ga]Ga-NODAGA-TriGalactan shows high in vitro stability and selectively binds to the ASGR allowing imaging of the functional liver mass with high contrast. Thus, our first generation compound resulted already in an alternative to 99mTc-GSA for imaging the functional liver reserve and might allow the broader use of this imaging technique. [ABSTRACT FROM AUTHOR]

Background: Glycosylation is an enzyme-catalyzed post-translational modification that is distinct from glycation and is present on a majority of plasma proteins. N-glycosylation occurs on asparagine residues predominantly within canonical N-glycosylation motifs (Asn-X-Ser/Thr) although non-canonical N-glycosylation motifs Asn-X-Cys/Val have also been reported. Albumin is the most abundant protein in plasma whose glycation is well-studied in diabetes mellitus. However, albumin has long been considered a non-glycosylated protein due to absence of canonical motifs. Albumin contains two non-canonical N-glycosylation motifs, of which one was recently reported to be glycosylated. Methods: We enriched abundant serum proteins to investigate their N-linked glycosylation followed by trypsin digestion and glycopeptide enrichment by size-exclusion or mixed-mode anion-exchange chromatography. Glycosylation at canonical as well as non-canonical sites was evaluated by liquid chromatography–tandem mass spectrometry (LC–MS/MS) of enriched glycopeptides. Deglycosylation analysis was performed to confirm N-linked glycosylation at non-canonical sites. Albumin-derived glycopeptides were fragmented by MS3 to confirm attached glycans. Parallel reaction monitoring was carried out on twenty additional samples to validate these findings. Bovine and rabbit albumin-derived glycopeptides were similarly analyzed by LC–MS/MS. Results: Human albumin is N-glycosylated at two non-canonical sites, Asn68 and Asn123. N-glycopeptides were detected at both sites bearing four complex sialylated glycans and validated by MS3-based fragmentation and deglycosylation studies. Targeted mass spectrometry confirmed glycosylation in twenty additional donor samples. Finally, the highly conserved Asn123 in bovine and rabbit serum albumin was also found to be glycosylated. Conclusions: Albumin is a glycoprotein with conserved N-linked glycosylation sites that could have potential clinical applications. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-alpha (TNF-α) serves as a crucial biomarker in various diseases, necessitating sensitive detection methodologies. This study introduces an innovative approach utilizing an aptamer-functionalized surface plasmon resonance (SPR) substrate together with an ultrasensitive measure, the Goos–Hänchen (GH) shift, to achieve sensitive detection of TNF-α. The developed GH-aptasensing platform has shown a commendable figure-of-merit of 1.5 × 104 μm per RIU, showcasing a maximum detectable lateral position shift of 184.7 ± 1.2 μm, as characterized by the glycerol measurement. Employing aptamers as the recognition unit, the system exhibits remarkable biomolecule detection capabilities, including the experimentally obtained detection limit of 1 aM for the model protein bovine serum albumin (BSA), spanning wide dynamic ranges. Furthermore, the system successfully detects TNF-α, a small cytokine, with an experimental detection limit of 1 fM, comparable to conventional SPR immunoassays. This achievement represents one of the lowest experimentally derived detection limits for cytokines in aptamer-based SPR sensing. Additionally, the application of the GH shift marks a ground breaking advancement in aptamer-based biosensing, holding significant promise for pushing detection limits further, especially for small cytokine targets. [ABSTRACT FROM AUTHOR]

Currently, there are no accurate means to predict spontaneous preterm birth (SPTB). Recently, we observed low expression of alpha-1 antitrypsin (AAT) in SPTB placentas. Present aim was to compare the concentrations of maternal serum AAT in pregnancies with preterm and term deliveries. Serum C-reactive protein (CRP) was used as a reference inflammatory marker. Two populations were studied. The first population comprised women who eventually gave birth spontaneously preterm (SPTB group) or term (control group). The second population included pregnant women shortly before delivery and nonpregnant women. We observed that serum AAT levels were higher in the SPTB group than in the controls, and a similar difference was observed when serum CRP was considered in multivariable analysis. However, the overlap in the AAT concentrations was considerable. No statistical significance was observed in serum AAT levels between preterm and term pregnancies at delivery. However, AAT levels were higher at delivery compared to nonpregnant controls. We did not observe a strong correlation between serum AAT and CRP in early pregnancy samples and at labor. We propose that during early pregnancy, complicated by subsequent SPTB, modest elevation of serum AAT associates with SPTB. [ABSTRACT FROM AUTHOR]

Background: Understanding the molecular mechanisms of Alzheimer's disease (AD) has important clinical implications for guiding therapy. Impaired amyloid beta (Aβ) clearance is critical in the pathogenesis of sporadic AD, and blood monocytes play an important role in Aβ clearance in the periphery. However, the mechanism underlying the defective phagocytosis of Aβ by monocytes in AD remains unclear. Methods: Initially, we collected whole blood samples from sporadic AD patients and isolated the monocytes for RNA sequencing analysis. By establishing APP/PS1 transgenic model mice with monocyte-specific cystatin F overexpression, we assessed the influence of monocyte-derived cystatin F on AD development. We further used a nondenaturing gel to identify the structure of the secreted cystatin F in plasma. Flow cytometry, enzyme-linked immunosorbent assays and laser scanning confocal microscopy were used to analyse the internalization of Aβ by monocytes. Pull down assays, bimolecular fluorescence complementation assays and total internal reflection fluorescence microscopy were used to determine the interactions and potential interactional amino acids between the cystatin F protein and Aβ. Finally, the cystatin F protein was purified and injected via the tail vein into 5XFAD mice to assess AD pathology. Results: Our results demonstrated that the expression of the cystatin F protein was specifically increased in the monocytes of AD patients. Monocyte-derived cystatin F increased Aβ deposition and exacerbated cognitive deficits in APP/PS1 mice. Furthermore, secreted cystatin F in the plasma of AD patients has a dimeric structure that is closely related to clinical signs of AD. Moreover, we noted that the cystatin F dimer blocks the phagocytosis of Aβ by monocytes. Mechanistically, the cystatin F dimer physically interacts with Aβ to inhibit its recognition and internalization by monocytes through certain amino acid interactions between the cystatin F dimer and Aβ. We found that high levels of the cystatin F dimer protein in blood contributed to amyloid pathology and cognitive deficits as a risk factor in 5XFAD mice. Conclusions: Our findings highlight that the cystatin F dimer plays a crucial role in regulating Aβ metabolism via its peripheral clearance pathway, providing us with a potential biomarker for diagnosis and potential target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

The eukaryotic p24 family, consisting of α-, β-, γ- and δ-p24 subfamilies, has long been known to be involved in regulating secretion. Despite increasing interest in these proteins, fundamental questions remain about their role. Here, we systematically investigated Drosophila p24 proteins. We discovered that members of all four p24 subfamilies are required for general secretion and that their localizations between ER exit site (ERES) and Golgi are interdependent in an α→βδ→γ sequence. We also found that localization of p24 proteins and ERES determinant Tango1 requires interaction through their respective GOLD and SH3 lumenal domains, with Tango1 loss sending p24 proteins to the plasma membrane and vice versa. Finally, we show that p24 loss expands the COPII zone at ERES and increases the number of ER-Golgi vesicles, supporting a restrictive role of p24 proteins on vesicle budding for efficient transport. Our results reveal Tango1-p24 interplay as central to the generation of a stable ER-Golgi interface. [ABSTRACT FROM AUTHOR]

Background: The association between the systemic immune-inflammation index (SII) and the serum soluble-Klotho concentration (pg/ml) in osteoarthritis (OA) patients is unknown. This study aimed to investigate the relationship between the SII and serum soluble-Klotho levels in OA patients. Methods: All study data were obtained from the National Health and Nutrition Examination Survey (NHANES) database (n = 1852 OA patients; age range = 40–79 years). The SII and serum Klotho measurement data are from the NHANES mobile examination centre. The SII values were divided into quartiles (Q1-4: 0.02–3.36, 3.36–4.78, 4.79–6.70, and 6.70–41.75). A multivariate linear regression model was constructed to evaluate the association between the SII and serum Klotho levels in OA patients; interaction tests were conducted to test the stability of the statistical results. Results: Multivariate linear regression revealed a negative linear relationship between the SII and serum Klotho concentration in OA patients (β = -6.05; 95% CI: -9.72, -2.39). Compared to Q1, Q4 was associated with lower serum Klotho concentrations (β = -59.93; 95% CI: -96.57, -23.28). Compared with that of Q1, the β value of Q2-Q4 showed a downwards trend as the SII increased (Ptrend <0.001). The stratified analysis results indicated that the SII had a greater sensitivity in predicting serum Klotho concentrations in OA patients aged 60–79 years (Pinteraction = 0.028). Conclusions: There was a significant negative linear correlation between the SII and serum Klotho concentration in OA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in OA patients. Klotho may be a potential anti-inflammatory drug for OA treatment. [ABSTRACT FROM AUTHOR]

Diabetic individuals with diabetic cardiomyopathy (DbCM) present with abnormal myocardial structure and function. DbCM cannot be accurately diagnosed due to the lack of suitable diagnostic biomarkers. In this study, 171 eligible participants were divided into a healthy control (HC), type 2 diabetes mellitus (T2DM) patients without DbCM (T2DM), or DbCM group. Serum fibrinogen-like protein 1 (FGL-1) and other biochemical parameters were determined for all participants. Serum FGL-1 levels were significantly higher in patients with DbCM compared with those in the T2DM group and HCs. Serum FGL-1 levels were negatively correlated with left ventricular fractional shortening and left ventricular ejection fraction (LVEF) and positively correlated with left ventricular mass index in patients with DbCM after adjusting for age, sex and body mass index. Interaction of serum FGL-1 and triglyceride levels on LVEF was noted in patients with DbCM. A composite marker including serum FGL-1 and triglycerides could differentiate patients with DbCM from those with T2DM and HCs with an area under the curve of 0.773 and 0.789, respectively. Composite marker levels were negatively correlated with N-terminal B-type natriuretic peptide levels in patients with DbCM. Circulating FGL-1 may therefore be a valuable index reflecting cardiac functions in DbCM and to diagnose DbCM. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. Methods: 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. Results: 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The β-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. Conclusion: This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets. Methods: Based on publicly available genome‐wide association study summary statistics, we employed a two‐sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset. Results: MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase‐activating protein 1 [RGAP1], IL‐21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype‐wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes. Conclusion: Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Serum protein electrophoresis (SPEP) is a valuable laboratory test that separates proteins from the blood based on their electrical charge and size. the test can detect and analyze various protein abnormalities, and the interpretation of graphic SPEP features plays a crucial role in the diagnosis and monitoring of conditions, such as myeloma. Furthermore, the advancement of artificial intelligence (AI) technology presents an opportunity to enhance the organization and optimization of analytical procedures by streamlining the process and reducing the potential for human error in SPeP analysis, thereby making the process more efficient and reliable. For instance, AI can assist in the identification of protein peaks, the calculation of their relative proportions, and the detection of abnormalities or inconsistencies. this review explores the characteristics and limitations of AI in SPEP, and the role of standardization in improving its clinical utility. It also offers guidance on the rational ordering and interpreting of SPeP results in conjunction with AI. Such integration can effectively reduce the time and resources required for manual analysis while improving the accuracy and consistency of the results. [ABSTRACT FROM AUTHOR]

Longitudinal evolution of peritoneal protein loss (PPL), a reflection of hydrostatic pressure–driven leak of plasma proteins through the large-pore pathway, is not clear. Time on PD causes loss of mesothelial cells, vasculopathy, and increased thickness of the submesothelial fibrous layer. Are these structural changes associated with progressive increase of PPL, in a parallel with the rise in the D/P creatinine? The aim of the present study was to identify longitudinal changes of PPL over time. This single-center, longitudinal study included 52 peritoneal dialysis (PD) patients with a median follow-up of 26.5 months, evaluated at two different time points with a minimum interval of 6 months. Repeated measures analysis was performed using paired sample t-test or the nonparametric Wilcoxon signed-rank test, depending on the distribution. After a median interval of 15.5 months, lower levels of residual renal function and urine volume, lower Kt/V, and creatinine clearance were found. D/P creatinine and PPL were stable, but a decrease in ultrafiltration was present. Systemic inflammation, nutrition, and volume overload showed no significant change with time on PD. Analysis of a subpopulation with over 48 months between initial and subsequential assessment (n = 11) showed again no difference in inflammation, nutritional and hydration parameters from baseline, but importantly PPL decreased after more than 4 years on PD (mean difference 1.2 g/24, p = 0.033). D/P creatinine and dip of sodium remained unchanged. The absence of deleterious effects of time on PD is reassuring, pointing to the benefit of updated PD prescription, including the standard use of more biocompatible solutions towards membrane preservation and adjusted prescription avoiding overhydration and inflammation while maintaining nutritional status. After controlling for confounders, PPL may act as a biomarker of acquired venous vasculopathy, even if small pore fluid transport rates and free water transport are preserved. [ABSTRACT FROM AUTHOR]

The L 1 region of bovine adenovirus (BAdV)-3 encodes a multifunctional protein named protein VII. Anti-protein VII sera detected a protein of 26 kDa in transfected or BAdV-3-infected cells, which localizes to nucleus and nucleolus of infected/transfected cells. Analysis of mutant protein VII identified four redundant overlapping nuclear/nucleolar localization signals as deletion of all four potential nuclear/nucleolar localization signals localizes protein VII predominantly to the cytoplasm. The nuclear import of protein VII appears to use importin α (α-1), importin-β (β-1) and transportin-3 nuclear transport receptors. In addition, different nuclear transport receptors also require part of protein VII outside nuclear localization sequences for efficient interaction. Proteomic analysis of protein complexes purified from recombinant BAdV-3 expressing protein VII containing Strep Tag II identified potential viral and cellular proteins interacting with protein VII. Here, we confirm that protein VII interacts with IVa2 and protein VIII in BAdV-3-infected cells. Moreover, amino acids 91–101 and 126–137, parts of non-conserved region of protein VII, are required for interaction with IVa2 and protein VIII, respectively. [ABSTRACT FROM AUTHOR]

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6–18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic manifestations and/or obstetric complications in patients with persistently positive antiphospholipid antibodies (aPL). aPL are a heterogeneous group of autoantibodies, but only lupus anticoagulant, anticardiolipin (aCL), and antibeta2‐glycoprotein I antibodies (aβ2GPI) IgG or IgM are included as laboratory classification criteria. Seronegative APS patients are usually defined as patients with the clinical symptoms of APS but who test negative for aPL. The negativity to classic aPL criteria does not exclude the presence of other aPL. Several noncriteria aPL have been identified. Some noncriteria aPL are well studied, such as IgA aCL and aβ2GPI, the antiphosphatidylserine‐prothrombin (aPS/PT) antibodies, and the antibodies against the domain I of beta2‐glycoprotein I (aDI), both latter groups receiving more attention for their role in thrombotic events and pregnancy complications. Other noncriteria aPL that have been studied are antibodies against annexin V, prothrombin, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin‐cardiolipin complex, anti‐protein S/protein C. Measurement of some of these noncriteria aPL (aPS/PT, aDI) is useful in the laboratory work‐out of APS in specific situations. We have to differentiate between patients who are positive for noncriteria aPL only, and patients who have both criteria and noncriteria aPL to enable us to study their role in the diagnosis or risk stratification of APS. The research on noncriteria aPL is continually developing as the clinical relevance of these antibodies is not yet fully clarified. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. Methods: 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. Results: 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The β-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. Conclusion: This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP. [ABSTRACT FROM AUTHOR]

Background: Peritoneal fluid lactate concentration is an important diagnostic tool in horses with abdominal pain. Information on peritoneal lactate concentrations is lacking following parturition in the mare. Objectives: To compare blood and peritoneal lactate concentrations in a population of mares within 36 h post‐partum, report a normal reference range and identify any impact of retained foetal membranes (RFMs). Methods: This is a retrospective study evaluating healthy mares from which blood and peritoneal samples had been obtained within 36 h of parturition. Exclusion criteria included signs of abdominal pain within this period. Data was interrogated for normality using a Shapiro–Wilk test. Wilcoxon signed‐rank test and Bland–Altman analysis were used to compare blood and peritoneal lactate concentrations. Linear regression was used to compare age and breed data with peritoneal lactate concentrations. Significance was defined as p < 0.05. Results: Forty mares met the inclusion criteria. Mean age was 12.6 ± 4.1 years, and most mares were multiparous (65%). Peritoneal lactate ((1.2 (IQR = 0.9–1.6) mmol/L) was increased compared to blood lactate concentration (0.7 (IQR = 0–1.1)mmol/L; p < 0.001). Plasma total protein (TP) concentrations were 68 (IQR = 64–74) g/L and peritoneal protein concentrations 8 (IQR = 4–9.7) g/L. Six mares developed RFM. The median fold‐increase in peritoneal lactate concentration compared to blood lactate concentration was 0.9 (IQR: 0.01–1.7; range: 0–2.5). The reference range for peritoneal fluid lactate concentration was 0–2.5 mmol/L. Conclusion: Peritoneal lactate concentrations in healthy post‐partum mares remained within the normal reference range and were not influenced by RFM or parturition. Increased peritoneal lactate in this group warrants further investigation. [ABSTRACT FROM AUTHOR]

Objective: Alzheimer's disease (AD) is characterized by the progressive degeneration and damage of neurons in the brain. However, developing an accurate diagnostic assay using blood samples remains a challenge in clinic practice. The aim of this study was to explore senescence‐associated secretory phenotypes (SASPs) in peripheral blood using mass spectrometry based multi‐omics approach and to establish diagnostic assays for AD. Methods: This retrospective study included 88 participants, consisting of 29 AD patients and 59 cognitively normal (CN) individuals. Plasma and serum samples were examined using high‐resolution mass spectrometry to identify proteomic and metabolomic profiles. Receiver operating characteristic (ROC) analysis was employed to screen biomarkers with diagnostic potential. K‐nearest neighbors (KNN) algorithm was utilized to construct a multi‐dimensional model for distinguishing AD from CN. Results: Proteomics analysis revealed upregulation of five plasma proteins in AD, including RNA helicase aquarius (AQR), zinc finger protein 587B (ZNF587B), C‐reactive protein (CRP), fibronectin (FN1), and serum amyloid A‐1 protein (SAA1), indicating their potential for AD classification. Interestingly, KNN‐based three‐dimensional model, comprising AQR, ZNF587B, and CRP, demonstrated its high accuracy in AD recognition, with evaluation possibilities of 0.941, 1.000, and 1.000 for the training, testing, and validation datasets, respectively. Besides, metabolomics analysis suggested elevated levels of serum phenylacetylglutamine (PAGIn) in AD. Interpretation: The multi‐omics outcomes highlighted the significance of the SASPs, specifically AQR, ZNF587B, CRP, and PAGIn, in terms of their potential for diagnosing AD and suggested neuronal aging‐associated pathophysiology. [ABSTRACT FROM AUTHOR]

Introduction: German cockroach (GCr) aeroallergens are associated with allergic rhinitis and asthma. Vitellogenin (Vg) and vitellin (Vn) are abundant proteins in GCr blood and eggs (including egg cases), respectively, and are possible high molecular mass allergens. Prior efforts to purify Vg/Vn yielded amounts too small for subsequent studies. In this study, we report the affinity purification of Vg/Vn from whole-body defatted GCr powder and determination of the binding of Vg/Vn to anti-GCr IgE. Method: New Zealand white rabbits were immunized with pure Vg/Vn in Freund's adjuvant, and IgG was purified from the rabbit sera and conjugated to cyanogen bromide (CNBr)-activated Sepharose. Aqueous extracts from GCr powder were passed over the column. After extensive washing, putative Vg/Vn was eluted in low-pH buffer, neutralized, and analyzed by SDS-PAGE and liquid chromatography high-resolution mass spectrometry (LC-HRMS). IgE binding of Vg/Vn was evaluated by inhibition of IgE binding to GCr-ImmunoCAP(I6) in sera from 10 GCr-allergic individuals. In addition, Vg/Vn was biotinylated and bound to ImmunoCAP-streptavidin, and direct IgE antibody binding to the immobilized Vg/Vn was determined in sera from 26 GCr-allergic individuals. Results: Vg/Vn isolated by affinity chromatography was 91% pure by LC-HRMS; contaminants included Bla g 3 (0.9%), human keratin (6%), and rabbit IgG. Vg/Vn inhibited IgE binding to GCr-ImmunoCAP(I6) in 8 of 10 sera. In direct-binding experiments, 21/26 (80%) sera had anti-Vg/Vn IgE at>0.10 kUA/L, while 11/26 (42%) sera were>0.35 kUA/L. Conclusions: We affinity-purified Vg/Vn and demonstrated that Vg/Vn-specific IgE antibody is a major component of GCr-specific IgE. [ABSTRACT FROM AUTHOR]

Glomerular hyperfiltration (GH) has been reported to be higher in women with polycystic ovary syndrome (PCOS) and is an independent risk factor for renal function deterioration, metabolic, and cardiovascular disease. The aim of this study was to determine GH in type A PCOS subjects and to identify whether inflammatory markers, markers of CKD, renal tubule injury markers, and complement system proteins were associated. In addition, a secondary cohort study was performed to determine if the eGFR had altered over time. In this comparative cross-sectional analysis, demographic, metabolic, and proteomic data from Caucasian women aged 18–40 years from a PCOS Biobank (137 with PCOS, 97 controls) was analyzed. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for inflammatory proteins, serum markers of chronic kidney disease (CKD), tubular renal injury markers, and complement system proteins. A total of 44.5% of the PCOS cohort had GH (eGFR ≥ 126 mL/min/1.73 m2 (n = 55)), and 12% (n = 17) eGFR ≥ 142 mL/min/1.73 m2 (super-GH(SGH)). PCOS-GH women were younger and had lower creatinine and urea versus PCOS-nonGH. C-reactive protein (CRP), white cell count (WCC), and systolic blood pressure (SBP) were higher in PCOS versus controls, but CRP correlated only with PCOS-SGH alone. Complement protein changes were seen between controls and PCOS-nonGH, and decay-accelerator factor (DAF) was decreased between PCOS-nonGH and PCOS-GSGH (p < 0.05). CRP correlated with eGFR in the PCOS-SGH group, but not with other inflammatory or complement parameters. Cystatin-c (a marker of CKD) was reduced between PCOS-nonGH and PCOS-GSGH (p < 0.05). No differences in tubular renal injury markers were found. A secondary cohort notes review of the biobank subjects 8.2–9.6 years later showed a reduction in eGFR: controls −6.4 ± 12.6 mL/min/1.73 m2 (−5.3 ± 11.5%; decrease 0.65%/year); PCOS-nonGH −11.3 ± 13.7 mL/min/1.73 m2 (−9.7 ± 12.2%; p < 0.05, decrease 1%/year); PCOS-GH (eGFR 126–140 mL/min/17.3 m2) −27.1 ± 12.8 mL/min/1.73 m2 (−19.1 ± 8.7%; p < 0.0001, decrease 2%/year); PCOS-SGH (eGFR ≥ 142 mL/min/17.3 m2) −33.7 ± 8.9 mL/min/17.3 m2 (−22.8 ± 6.0%; p < 0.0001, decrease 3.5%/year); PCOS-nonGH eGFR versus PCOS-GH and PCOS-SGH, p < 0.001; no difference PCOS-GH versus PCOS-SGH. GH was associated with PCOS and did not appear mediated through tubular renal injury; however, cystatin-c and DAF were decreased, and CRP correlated positively with PCOS-SGH, suggesting inflammation may be involved at higher GH. There were progressive eGFR decrements for PCOS-nonGH, PCOS-GH, and PCOS-SGH in the follow-up period which, in the presence of additional factors affecting renal function, may be clinically important in the development of CKD in PCOS. [ABSTRACT FROM AUTHOR]

The escalating prevalence of metabolic disorders, notably type 2 diabetes (T2D) and obesity, presents a critical global health challenge, necessitating deeper insights into their molecular underpinnings. Our study integrates proteomics and metabolomics analyses to delineate the complex molecular landscapes associated with T2D and obesity. Leveraging data from 130 subjects, including individuals with T2D and obesity as well as healthy controls, we elucidate distinct molecular signatures and identify novel biomarkers indicative of disease progression. Our comprehensive characterization of cardiometabolic proteins and serum metabolites unveils intricate networks of biomolecular interactions and highlights differential protein expression patterns between T2D and obesity cohorts. Pathway enrichment analyses reveal unique mechanisms underlying disease development and progression, while correlation analyses elucidate the interplay between proteomics, metabolomics, and clinical parameters. Furthermore, network analyses underscore the interconnectedness of cardiometabolic proteins and provide insights into their roles in disease pathogenesis. Our findings may help to refine diagnostic strategies and inform the development of personalized interventions, heralding a new era in precision medicine and healthcare innovation. Through the integration of multi-omics approaches and advanced analytics, our study offers a crucial framework for deciphering the intricate molecular underpinnings of metabolic disorders and paving the way for transformative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objectives: Although elevated serum immunoglobulin A (IgA) levels are thought to exclude a diagnosis of IgG4-related disease (IgG4-RD), IgG4-RD has been definitively diagnosed in some patients despite elevated serum IgA levels. This study aimed to clarify the prevalence of elevated IgA levels in patients with IgG4-RD and to compare the clinical features of IgG4-RD patients with and without elevated IgA levels. Methods: The clinical features of 169 IgG4-RD patients were retrospectively compared among those with and without elevated serum IgA levels. Results: Of the 169 patients with IgG4-RD, 17 (10.1%) had elevated serum IgA levels. Those with elevated serum IgA levels showed higher serum C-reactive protein levels and lower prevalence of relapse than those without. Other clinical features did not differ significantly, including inclusion scores of the American College of Rheumatology/European League Against Rheumatism classification criteria. Cox regression analysis showed that elevated serum IgA levels were associated with a lower incidence of relapse. Moreover, patients with elevated serum IgA levels showed prompt improvement in response to glucocorticoids in the IgG4-RD responder index. Conclusions: Some patients diagnosed with IgG4-RD have high serum IgA levels. These patients may form a subgroup, characterized by good response to glucocorticoids, less frequent relapse, mildly elevated serum C-reactive protein levels, and possible complications of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Context: Timely pregnancy diagnosis is critical for reducing non-production days and improving the reproductive efficiency of sheep flocks. Aims: The aim of this study was to investigate the serum proteomic profile of ewes in different gestational stages and explore the potential of differentially expressed proteins as biomarkers for early gestation. Methods: Serum samples were collected from two groups: pregnant sheep (n = 4) and non-pregnant sheep (n = 4) on Day 14 after mating. The differentially expressed proteins were detected using tandem mass-tag (TMT) labelling with liquid chromatography tandem-mass spectrometry. The differentially expressed proteins were confirmed using enzyme-linked immunosorbent assay (ELISA). Furthermore, six selected proteins were evaluated in ewes (n = 35) on Day 14 from mating by using ELISA to assess their potential as biomarkers for early pregnancy. Receiver-operating characteristic (ROC) curves were used to analyse the diagnostic accuracy of these proteins. Key results: Twenty proteins, of a total of 555 proteins detected, showed differential expression between pregnant and non-pregnant sheep. From the ROC-curve data, CHI3L1 (AUC = 0.992), PSMB4 (AUC = 0.976) and LGALS3BP (AUC = 0.844) had high predictive value in the diagnosis of early pregnancy. Conclusions: In this study, CHI3L1, PSMB4 and LGALS3BP were found to be differentially expressed proteins in the serum of pregnant sheep. Therefore, these three proteins carry a high probability as candidate biomarkers for early gestational embryo attachment in ewes. Implications: Early pregnancy diagnosis enables timely identification of non-pregnant ewes, resulting in optimised resource allocation and enhanced economic benefits for farmers by reducing production costs. The present study enables to advance the diagnosis of pregnancy in ewes to the first oestrous period after breeding. The differentially expressed protein in serum was found to be a highly specific and sensitive biomarker for early pregnancy diagnosis in ewes. Its application in production can reduce the number of days of mating loss in ewes, reduce production costs and improve economic efficiency. [ABSTRACT FROM AUTHOR]

The supplementation of aquafeed with probiotics is recommended for feasible aquaculture activities. Therefore, the aim of current study was to investigate the potential effects of probiotics on growth performance, feed utilization, biochemical attributes, redox status and immunity response as well as the transcription of heat‐shock protein 70 (HSP70) and insulin‐like growth factor‐1 (IGF‐1) genes of Nile tilapia (Oreochromis niloticus; n = 120). Fish with an initial weight of 8.17 ± 0.02 g/fish were randomly divided into four treatment groups and were fed diets containing 0, 0.5, 1 and 1.5 mg immunobacteryne (IMB)/kg diet respectively. Dietary IMB at 1.5 g/kg diet significantly improved the growth performance, feed consumption and growth hormone secretion of the experimental fish (p < 0.05). The 1 or 1.5 g IMB/kg diet boosted phagocytic activities and innate immune response. Serum total protein, total cholesterol, triglycerides and glucose were significantly increased in the groups that were fed 1 and 1.5 mg IMB/kg diet compared to the control (p < 0.05). Meanwhile, the levels of uric acid, creatinine, liver enzymes (aspartate transaminase and alanine transaminase) and cortisol hormone were significantly reduced in the aforementioned treated groups compared to the control (p < 0.05). All fish fed IMB‐supplemented diet showed a significant increase in the expression of IGF‐1 gene, while the transcription of HSP70 was significantly decreased (p < 0.05). In conclusion, the dietary inclusion of IMB (1 g/kg diet) enhanced growth promoters, feed efficacy, blood biochemical, redox balance and nonspecific immune responses in Nile tilapia fingerlings. [ABSTRACT FROM AUTHOR]

Background: The complement system plays crucial roles in cognitive impairment and acute ischemic stroke (AIS). High levels of complement proteins in plasma astrocyte-derived exosomes (ADEs) were proven to be associated with Alzheimer's disease. We aimed to investigate the relationship of complement proteins in serum ADEs with poststroke cognitive impairment in type 2 diabetes mellitus (T2DM) patients. Methods: This study analyzed 197 T2DM patients who suffered AIS. The Beijing version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Complement proteins in serum ADEs were quantified using ELISA kits. Results: Mediation analyses showed that C5b-9 and C3b in serum ADEs partially mediate the impact of obstructive sleep apnea (OSA), depression, small vessel disease (SVD), and infarct volume on cognitive function at the acute phase of AIS in T2DM patients. After adjusting for age, sex, time, and interaction between time and complement proteins in serum ADEs, the mixed linear regression showed that C3b and complement protein Factor B in serum ADEs were associated with MoCA scores at three-, six-, and twelve-months after AIS in T2DM patients. Conclusions: Our study suggested that the impact of OSA, depression, SVD, and infarct volume on cognitive impairment in the acute stage of AIS may partially mediate through the complement proteins in serum ADEs. Additionally, the complement proteins in serum ADEs at the acute phase of AIS associated with MoCA scores at three-, six-, twelve months after AIS in T2DM patients. REGISTRATION: URL: [ABSTRACT FROM AUTHOR]

The approach toward the molecular imprinting of hydrogel with different proteins erects the template-size cavities inside the matrix. The cavities provide the binding sites to adsorb the protein perfectly in the hydrogel. To intensify the adsorption efficiency of protein bovine serum albumin (BSA), cobalt ions (Co) play an essential role. In contrast, 2-(Dimethylamino) ethyl methacrylate (DMAEMA) provides pH sustainability as an assistant monomer. Results elucidate that incorporating Co in preparation can enhance the hydrogel's imprinting effect or adsorption efficiency compared to others due to the development of coordinated covalent bonding. Hydrogel adsorption capacity is an essential factor in this study. In this research, the obtained BSA-imprinted hydrogel also observed a high protein adsorption capacity. The Co concentration and pH of the hydrogel system are the main factors affecting proteins' adsorption efficiency. Their optimizations are the main concerns, and their successful implementations are confirmed by UV/Vis spectroscopy. The imprinted BSA protein was removed by using 500 mmol/L NaCl solution. The two and three-parameter isothermal models were implemented to predict the mechanism of the adsorption process. [ABSTRACT FROM AUTHOR]

Heat stress (HS) during the dry period of dairy cows in hot and dry conditions compromises the physiological status and mammary gland development of dairy cows, thereby negatively affecting milk component yield in the subsequent lactation. Our objective was to evaluate the effects of cooling Holstein cows under moderate or higher HS conditions (i.e., ambient temperature higher than 30 °C, with a temperature-humidity index of 78.2 units) during the dry period on prepartum physiological status, postpartum productivity, and calf growth. Twenty-four multiparous Holstein cows were divided into two groups: one with a cooling system based on spray and fans under a pen shade (CL, n = 12) and the other not-cooled (NC, n = 12). The cooling system operated 10 h/d (09:00–19:00 h) for 60 d prepartum. During the morning, rectal temperature and respiration frequency were lower in CL cows, but not in the afternoon, which was attributed to higher (P < 0.01) dry matter intake by CL cows. Total serum protein was higher (P < 0.01) in CL cows, but hemoglobin was higher in NC cows (P < 0.01), with no differences in other electrolytes, hormones, hematological components, and metabolites. Milk fat and fat and fat-protein corrected milk were higher (P < 0.05) in CL cows. Female and birth weight trended (P = 0.08) to be higher in CL cows. Cooling cows during the dry period had a limited effect on physiology prepartum but increased postpartum productivity of Holstein cows under hot and dry conditions. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are a class of over 8000 chemicals, many of which are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet experimental binding data is limited to only a few PFAS congeners. Previously, we demonstrated the usefulness of a high-throughput, in vitro differential scanning fluorimetry assay for determination of relative binding affinities of human serum albumin for 24 PFAS congeners from 6 chemical classes. In the current study, we used this assay to comparatively examine differences in human, bovine, porcine, and rat serum albumin binding of 8 structurally informative PFAS congeners from 5 chemical classes. With the exception of the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorooctanol (6:2 FTOH), each PFAS congener bound by human serum albumin was also bound by bovine, porcine, and rat serum albumin. The critical role of the charged functional headgroup in albumin binding was supported by the inability of albumin of each species tested to bind 6:2 FTOH. Significant interspecies differences in serum albumin binding affinities were identified for each of the bound PFAS congeners. Relative to human albumin, perfluoroalkyl carboxylic and sulfonic acids were bound with greater affinity by porcine and rat serum albumin, and the perfluoroalkyl ether acid congener bound with lower affinity to porcine and bovine serum albumin. These comparative affinity data for PFAS binding by serum albumin from human, experimental model, and livestock species reduce critical interspecies uncertainty and improve accuracy of predictive bioaccumulation and toxicity assessments for PFAS. [ABSTRACT FROM AUTHOR]

Objective: We investigated the correlation between serum C1q/TNF-related protein 4 (CTRP4) level and flow-mediated dilation (FMD) in patients with type 2 diabetes mellitus (T2DM), and evaluated the biological effects of CTRP4 on human umbilical vein endothelial cells (HUVECs). Methods: A group of 165 patients diagnosed with T2DM were included in this study. Endothelial function was measured with the examination of brachial artery FMD. ELISA kit was used to measure the levels of CTRP4 in serum. HUVECs were stimulated with recombinant CTRP4 protein to assess its biological functions. Results: The levels of CTRP4 showed a significant variation among three groups based on FMD tertiles (p = 0.001). What's more, FMD had a significant difference among three CTRP4 tertile groups (p < 0.05) and was negatively related to serum CTRP4 levels (r = −0.270, p < 0.001). In T2DM patients, logistic regression analysis demonstrated that CTRP4 was the primary influence factor of low FMD (p < 0.01). In receiver operating characteristic curve analysis, the area under the curve of CTRP4 for predicting low FMD was 0.66 (95%CI 0.58–0.75). When stimulated HUVECs with recombinant CTRP4 protein, we found that CTRP4 could concentration-dependently ameliorate proliferation and migration of HUVECs in wounding healing and transwell assay. This protein could also decrease the expression of IL-6 and TNF-α and promote the release of NO in HUVEC supernatants, with suppression of NF-κB and STAT3 phosphorylation. Conclusions: Serum CTRP4 concentrations were negatively associated with FMD. CTRP4 alleviated proliferation, migration and inflammation in HUVECs through the suppression of NF-κB and STAT3 signaling pathways. [ABSTRACT FROM AUTHOR]

The bile salt export pump (ABCB11/BSEP) is a hepatocyte plasma membrane‐resident protein translocating bile salts into bile canaliculi. The sequence alignment of the four full‐length transporters of the ABCB subfamily (ABCB1, ABCB4, ABCB5 and ABCB11) indicates that the NBD‐NBD contact interface of ABCB11 differs from that of other members in only four residues. Notably, these are all located in the noncanonical nucleotide binding site 1 (NBS1). Substitution of all four deviant residues with canonical ones (quadruple mutant) significantly decreased the transport activity of the protein. In this study, we mutated two deviant residues in the signature sequence to generate a double mutant (R1221G/E1223Q). Furthermore, a triple mutant (E502S/R1221G/E1223Q) was generated, in which the deviant residues of the signature sequence and Q‐loop were mutated concurrently to canonical residues. The double and triple mutants showed 80% and 60%, respectively, of the activity of wild‐type BSEP. As expected, an increasing number of mutations gradually impair transport as an intricate network of interactions within the ABC proteins ensures proper functioning. [ABSTRACT FROM AUTHOR]

Background: Tubular dysfunction can cause electrolyte disturbances with potentially serious consequences. We studied the epidemiology and outcomes of electrolyte disturbances and tubular dysfunction among critically ill children and evaluated their relationships with acute kidney injury (AKI). Methods: We conducted a prospective cohort study recruiting children aged 1 month to ≤ 18 years old admitted to the pediatric intensive care unit (PICU) from 6/2020 to 6/2021. The serum levels of sodium, potassium, calcium, phosphate, and magnesium were reviewed and simultaneous urinary investigations for tubular function were performed among children with electrolyte disturbances. Results: Altogether there were 253 episodes of admission. The median (interquartile) age was 4.9 (1.3–11.0) years and 58.1% were male. The median number of electrolyte disorders was 3 (2–4) types. Hypophosphatemia (74.2%), hypocalcemia (70.3%) and hypermagnesemia (52.9%) were the three commonest types of disturbances. Urinary electrolyte wasting was commonly observed among children with hypomagnesemia (70.6%), hypophosphatemia (67.4%) and hypokalemia (28.6%). Tubular dysfunction was detected in 82.6% of patients and urinary β2-microglobulin level significantly correlated with the severity of tubular dysfunction (p < 0.001). The development of tubular dysfunction was independent of AKI status. Tubular dysfunction was associated with mortality (p < 0.001) and was an independent predictor of PICU length of stay (LOS) (p < 0.001). The incorporation of the tubular dysfunction severity into the AKI staging system improved the prediction of PICU LOS. Conclusions: Tubular dysfunction was associated with both morbidity and mortality in critically ill children and its assessment may help to capture a more comprehensive picture of acute kidney insult. [ABSTRACT FROM AUTHOR]

Transcranial histotripsy has shown promise as a non-invasive neurosurgical tool, as it has the ability to treat a wide range of locations in the brain without overheating the skull. One important effect of histotripsy in the brain is the blood–brain barrier (BBB) opening (BBBO) at the ablation site, but there is a knowledge gap concerning the extent of histotripsy-induced BBBO. Here we describe induction of BBBO by transcranial histotripsy and use of magnetic resonance imaging (MRI) and histology to quantify changes in BBBO at the periphery of the histotripsy ablation zone over time in the healthy mouse brain. An eight-element, 1 MHz histotripsy transducer with a focal distance of 32.5 mm was used to treat the brains of 23 healthy female BL6 mice. T1-gadolinium (T1-Gd) MR images were acquired immediately following histotripsy treatment and during each of the subsequent 4 wk to quantify the size and intensity of BBB leakage. The T1-Gd MRI results revealed that the hyperintense BBBO volume increased over the first week and subsided gradually over the following 3 wk. Histology revealed complete loss of tight junction proteins and blood vessels in the center of the ablation region immediately after histotripsy, partial recovery in the periphery of the ablation zone 1 wk following histotripsy and near-complete recovery of tight junction complex after 4 wk. These results provide the first evidence of transcranial histotripsy-induced BBBO and repair at the periphery of the ablation zone. [ABSTRACT FROM AUTHOR]

In this study cinnamaldehyde (CA) doped polyurethane cholesteryl pelargonate cholesteric liquid crystal composite membranes were produced and their properties were examined for use in biological applications. The relationship between the blood coagulation and protein adsorption was studied and the results showed that increasing CA concentration allowed an improvement in biological properties of them. Additionally, the effect of CA on the hyrophobicity of these membranes was investigated by determining water holding capacity, contact angles. The mechanical strength of these membranes were determined and it was found that their strength increased and the ability to elongate decreased with an increasing CA dopant concentration. [ABSTRACT FROM AUTHOR]

Elk-1 is a member of the ETS domain transcription factor superfamily that is phosphorylated upon mitogen-activated protein kinase (MAPK) pathway activation, which in turn regulated its interaction with partner protein serum response factor (SRF), leading to formation of a ternary complex with DNA. It has previously been reported that Elk-1 interacts with a mitotic kinase Aurora-A, although the mechanisms or the relevance of this interaction was unclear. Elk-1 was also reported to be phosphorylated by CDK5 on Thr417 residue. In this study, we show for the first time that this transcription factor interacts not only with Aurora-A but also with other mitotic kinases Aurora-B, Plk1, and Cdk1, and we define the interaction domain on Elk-1 to the first N-terminal 205 amino acids. We also describe putative phosphorylation sites of these mitotic kinases on Elk-1 and show that Elk-1 peptides containing these residues get phosphorylated by the mitotic kinases in in vitro kinase assays. We also perform bioinformatic analysis of mitotic phosphoproteomes and determine potential interaction partners for Elk-1 in Plk or Aurora phosphoproteomes. We propose that understanding the dynamic phosphorylation of Elk-1 by mitotic kinases is important and that it can present a novel target for anticancer strategies. [ABSTRACT FROM AUTHOR]