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Seaweed is multicellular marine macroalgae that enhances the immunity of aquatic organisms. The study was designed to assess the ethanolic extract (EtOH) extracted from red seaweed (Gracilariopsis lemaneiformis) on Nile tilapia (Oreochromis niloticus) to evaluate growth, immunity and haematological parameters. The EtOH was applied with fish feed in four treatments such as T1‐control (0% EtOH), T2 (5% w/v EtOH), T3 (10% w/v EtOH) and T4 (15% w/v EtOH) each with three replicates. The initial average weight of the fish was 17.53 ± 2.1 g. Results showed that the growth increased gradually with the percentage of red seaweed extract, whereas the mean weight gain was found significantly higher in T4 (51.5 ± 4.2) than in the control. The specific growth rate (%) and survival rate (%) were found higher in T4 at the lowest FCR compared to other treatments (p < 0.05). The blood haemoglobin level of Nile tilapia was higher in T4 (11.5 g/dL) and lowest recorded in T1 (7.5 g/dL). However, the level of blood glucose interacted inversely with blood haemoglobin. The plasma protein level was also varied among the treatments (p > 0.05). The blood parameters, refractive index (RI) and spleen somatic index (SSI) were significantly different among the treatments. The RI of blood plasma and SSI were found to be better in T4 treatment. The research indicated that red seaweed extracts significantly enhanced the growth and boosted the immunity level of Nile tilapia. [ABSTRACT FROM AUTHOR]

Abstract Purposes Gastric cancer (GC) is one of the most common malignant tumors threatening human beings and has a poor prognosis. Therefore, exploring unveiled biomarkers or therapeutic targets for the diagnosis and treatment of GC is crucial. Methods A total of 5772 protein quantitative trait loci (pQTL) were aggregated from four latest large-scale proteomics cohorts. Two-sample Mendelian randomization (two-sample MR) was utilized to identify the causal effect of blood plasma proteins on GC. Heterogeneity, pleiotropy, and directionality analyses were employed to evaluate proteins identified via two-sample MR. The robustness of results was further validated via colocalization. The drug targets of proteins were evaluated to reveal the compounds that can interfere with these proteins. Results Ten proteins with potential causations in relation to GC were identified: LY6D, SLURP1, MLN, PSCA, THSD1, CFTR, PPM1B, KDM3A, TSC1, and HCG22. Among these proteins, LY6D, SLURP1, and THSD1 were considered as the most reliable biomarkers of GC due to their significant H4 posterior probabilities in colocalization analysis and absence of pleiotropy. Compound 35, nitrosamide, and 0175029-0000 were potential drugs or small molecules targeting LY6D, SLURP1, and THSD1, respectively. Conclusion This study identified several plasma proteins as potential biomarkers of GC and provided data support and new insights into the early diagnosis, intervention, and therapeutic targets of GC.

Purposes: Gastric cancer (GC) is one of the most common malignant tumors threatening human beings and has a poor prognosis. Therefore, exploring unveiled biomarkers or therapeutic targets for the diagnosis and treatment of GC is crucial. Methods: A total of 5772 protein quantitative trait loci (pQTL) were aggregated from four latest large-scale proteomics cohorts. Two-sample Mendelian randomization (two-sample MR) was utilized to identify the causal effect of blood plasma proteins on GC. Heterogeneity, pleiotropy, and directionality analyses were employed to evaluate proteins identified via two-sample MR. The robustness of results was further validated via colocalization. The drug targets of proteins were evaluated to reveal the compounds that can interfere with these proteins. Results: Ten proteins with potential causations in relation to GC were identified: LY6D, SLURP1, MLN, PSCA, THSD1, CFTR, PPM1B, KDM3A, TSC1, and HCG22. Among these proteins, LY6D, SLURP1, and THSD1 were considered as the most reliable biomarkers of GC due to their significant H4 posterior probabilities in colocalization analysis and absence of pleiotropy. Compound 35, nitrosamide, and 0175029-0000 were potential drugs or small molecules targeting LY6D, SLURP1, and THSD1, respectively. Conclusion: This study identified several plasma proteins as potential biomarkers of GC and provided data support and new insights into the early diagnosis, intervention, and therapeutic targets of GC. [ABSTRACT FROM AUTHOR]

Background: Sepsis is an inflammatory disease that leads to severe mortality, highlighting the urgent need to identify new therapeutic strategies for sepsis. Proteomic research serves as a primary source for drug target identification. We employed proteome-wide Mendelian randomization (MR), genetic correlation analysis, and colocalization analysis to identify potential targets for sepsis and sepsis-related death. Methods: Genetic data for plasma proteomics were obtained from 35,559 Icelandic individuals and an initial MR analysis was conducted using 13,531 sepsis cases from the FinnGen R10 cohort to identify associations between plasma proteins and sepsis. Subsequently, significant proteins underwent genetic correlation analysis, followed by replication in 54,306 participants from the UK Biobank Pharma Proteomics Project and validation in 11,643 sepsis cases from the UK Biobank. The identified proteins were then subjected to colocalization analysis, enrichment analysis, and protein-protein interaction network analysis. Additionally, we also investigated a MR analysis using plasma proteins on 1,896 sepsis cases with 28-day mortality from the UK Biobank. Results: After FDR correction, MR analysis results showed a significant causal relationship between 113 plasma proteins and sepsis. Genetic correlation analysis revealed that only 8 proteins had genetic correlations with sepsis. In the UKB-PPP replication analysis, only 4 proteins were found to be closely associated with sepsis, while validation in the UK Biobank sepsis cases found overlaps for 21 proteins. In total, 30 proteins were identified in the aforementioned analyses, and colocalization analysis revealed that only 2 of these proteins were closely associated with sepsis. Additionally, in the 28-day mortality MR analysis of sepsis, we also found that only 2 proteins were significant. Conclusions: The identified plasma proteins and their associated metabolic pathways have enhanced our understanding of the complex relationship between proteins and sepsis. This provides new avenues for the development of drug targets and paves the way for further research in this field. [ABSTRACT FROM AUTHOR]

It remains challenging to translate the findings from genome-wide association studies (GWAS) of autoimmune diseases (AIDs) into interventional targets, presumably due to the lack of knowledge on how the GWAS risk variants contribute to AIDs. In addition, current immunomodulatory drugs for AIDs are broad in action rather than disease-specific. We performed a comprehensive protein-centric omics integration analysis to identify AIDs-associated plasma proteins through integrating protein quantitative trait loci datasets of plasma protein (1348 proteins and 7213 individuals) and totally ten large-scale GWAS summary statistics of AIDs under a cutting-edge systematic analytic framework. Specifically, we initially screened out the protein-AID associations using proteome-wide association study (PWAS), followed by enrichment analysis to reveal the underlying biological processes and pathways. Then, we performed both Mendelian randomization (MR) and colocalization analyses to further identify protein-AID pairs with putatively causal relationships. We finally prioritized the potential drug targets for AIDs. A total of 174 protein-AID associations were identified by PWAS. AIDs-associated plasma proteins were significantly enriched in immune-related biological process and pathways, such as inflammatory response (P = 3.96 × 10–10). MR analysis further identified 97 protein-AID pairs with potential causal relationships, among which 21 pairs were highly supported by colocalization analysis (PP.H4 > 0.75), 10 of 21 were the newly discovered pairs and not reported in previous GWAS analyses. Further explorations showed that four proteins (TLR3, FCGR2A, IL23R, TCN1) have corresponding drugs, and 17 proteins have druggability. These findings will help us to further understand the biological mechanism of AIDs and highlight the potential of these proteins to develop as therapeutic targets for AIDs. [ABSTRACT FROM AUTHOR]

Background: Peripheral neuropathy (PN) is a common neurological disorder, and circulating plasma proteins with causal genetic evidence are a major source of therapeutic targets. This study identifies several potential plasma proteins that are causally related to PN risk, providing new insights into protein-mediated pathogenesis of PN and potential targets for novel therapies. Methods: To identify potential therapeutic targets for PN, we employed twosample Mendelian randomization (MR) to identify plasma proteins associated with six common PN. First, we screened for proteins related to PN using genomewide association studies (GWAS), obtaining genetic data on plasma proteomes from 35,559 Icelanders. Summary data for six common PN, including Carpal Tunnel Syndrome (CTS), Trigeminal Neuralgia (TN), Alcoholic Neuropathy (AIP), Drug-induced Neuropathy (DIP), Diabetic Neuropathy (DP), and Guillain-Barré syndrome (GBS), were obtained from the FinnGen database. Two-sample MR and colocalization analyses were then conducted to further identify proteinPN pairs with presumed causal relationships. Enrichment analysis of positive proteins revealed potential biological processes and pathways. Based on druggene interaction analysis, we ultimately identified causal proteins associated with PN that could serve as potential drug targets for treating PN. Results: Through MR analysis, we identified eight proteins (UBC12, SEM4C, IL23R, Prothrombin, CBS, Microglobulin, MATN4, COLEC12) with causal relationships to PN. We found that UBC12 is a protective factor for DP and CTS, while the remaining proteins are risk factors. Further colocalization analysis showed a posterior probability of hypothesis 4 (PPH4) less than 0.75, indicating no positive colocalization results were found. From the pathway enrichment analysis, we discovered that the proteins were mainly concentrated in pathways related to defense response to bacterium, receptor signaling pathway via STAT, cell killing, negative regulation of cytokine production, and leukocyte mediated immunity. Finally, in Drug-Gene Interaction database (DGIdb), we identified three protein-coding genes (IL23R, F2, CBS) as potential drug targets for PN. Conclusion: Mendelian randomization studies confirm the causal relationship between genetically predicted PN-related risk and genetically predicted plasma protein abundance. Plasma proteins, as biomarkers associated with PN, can provide potential drug targets for etiological intervention research in PN. [ABSTRACT FROM AUTHOR]

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and sacroiliac joints. Recent genetic studies suggest certain plasma proteins may play a causal role in AS development. This study aims to identify and characterize these proteins using Mendelian randomization (MR) and colocalization analyses. Methods: Plasma protein data were obtained from recent publications in Nature Genetics, integrating data from five previous GWAS datasets, including 738 cispQTLs for 734 plasma proteins. GWAS summary data for AS were sourced from IGAS and other European cohorts. MR analyses were conducted using "TwoSampleMR" to assess causal links between plasma protein levels and AS. Colocalization analysis was performed with the coloc R package to identify shared genetic variants. Sensitivity analyses and protein-protein interaction (PPI) network analyses were conducted to validate findings and explore therapeutic targets. We performed Phenome-wide association study (PheWAS) to examine the potential side effects of drug protein on AS treatment. Results: After FDR correction, eight significant proteins were identified: IL7R, TYMP, IL12B, CCL8, TNFAIP6, IL18R1, IL23R, and ERAP1. Elevated levels of IL7R, IL12B, CCL8, IL18R1, IL23R, and ERAP1 increased AS risk, whereas elevated TYMP and TNFAIP6 levels decreased AS risk. Colocalization analysis indicated that IL23R, IL7R, and TYMP likely share causal variants with AS. PPI network analysis identified IL23R and IL7R as potential new therapeutic targets. Conclusions: This study identified eight plasma proteins with significant associations with AS risk, suggesting IL23R, IL7R, and TYMP as promising therapeutic targets. Further research is needed to explore underlying mechanisms and potential for drug repurposing. [ABSTRACT FROM AUTHOR]

The objective of this paper is to evaluate the effect of periodic exposure to formaldehyde in the anatomy laboratory on some plasma protein levels in male Wistar rats using appropriate standard procedures. Data obtained showed that formaldehyde air level were 0.06±0.00 ppm (parts per million) at the control site, 0.47±0.02 ppm in the dissection hall on non-dissection days, and 1.95±0.02 ppm in the dissection hall on dissection days. Plasma levels of albumin, globulin and fibrinogen were 4.76±0.13 g/l, 3.12±0.07 g/l and 1.04±0.16 g/l respectively on non-dissection days and 5.06±0.07 g/l, 3.24±0.06 g/l and 1.18±0.18 g/l respectively on dissection days. Results revealed significant increase in the atmospheric levels of formaldehyde in the dissection hall but the plasma protein levels showed no significant difference. In conclusion, exposure to formaldehyde in the Anatomy laboratory may not affect plasma protein levels in Wistar rats.

ABSTRACT Seaweed is multicellular marine macroalgae that enhances the immunity of aquatic organisms. The study was designed to assess the ethanolic extract (EtOH) extracted from red seaweed (Gracilariopsis lemaneiformis) on Nile tilapia (Oreochromis niloticus) to evaluate growth, immunity and haematological parameters. The EtOH was applied with fish feed in four treatments such as T1‐control (0% EtOH), T2 (5% w/v EtOH), T3 (10% w/v EtOH) and T4 (15% w/v EtOH) each with three replicates. The initial average weight of the fish was 17.53 ± 2.1 g. Results showed that the growth increased gradually with the percentage of red seaweed extract, whereas the mean weight gain was found significantly higher in T4 (51.5 ± 4.2) than in the control. The specific growth rate (%) and survival rate (%) were found higher in T4 at the lowest FCR compared to other treatments (p 0.05). The blood parameters, refractive index (RI) and spleen somatic index (SSI) were significantly different among the treatments. The RI of blood plasma and SSI were found to be better in T4 treatment. The research indicated that red seaweed extracts significantly enhanced the growth and boosted the immunity level of Nile tilapia.

Background: There is no evidence of peptides-probiotics symbiosis as supplements in aquafeeds. Aim: To evaluate the effect of peptides and probiotics supplementation via diet on blood parameters and growth performance of juvenile P. brachypomus, an Amazonian fish, during the growth-out phase. Methods: 120 juvenile P. brachypomus (242.77 g) were placed into twelve 200-L tanks (10 fish/tank), housed in an indoor open system with constant water renovation (flow rate:1.50 L/min). The experiment used a completely randomized design with a 4×5 factorial arrangement [4 doses of supplementation (CD: commercial diet; PepD: CD+1.50% of peptides per CD weight; ProD: CD+40.00 mL of activated probiotics per kg of diet (Lactobacillus spp., Rhodopseudomonas spp., Saccharomycetes spp.); PepProD: CD+Pep+Pro); 5 sampling times (0, 2nd, 4th, 6th, 8th week); n=3]. Fish were fed twice a day at a feeding rate of 1% of body weight. At each sampling time, blood was collected and fish were measured for growth performance analysis. Data was analyzed by using two-way ANOVA and Tukey's test (p0.05). Plasma glucose decreased for all fish in the 2nd week (59.56 mg/dL); then, that level increased in fish fed with the CD (89.00 mg/dL), while fish fed with PepD, ProD and PepProD showed constant values (57.22 mg/dL). The plasma protein levels were constant in fish fed with the PepD and PepProD, (p>0.05), while fish fed with the CD and ProD showed non-constant and higher values. At the end of the trial, fish fed with the PepProD showed the highest weight gain and the lowest feed conversion rate (39.66 g; 0.97). Conclusion: It is possible to maintain the stability of plasma glucose and plasma protein by supplementing diets with peptides, but the peptides-probiotics symbiosis administrated via diet contributes to maintain the stability of plasma glucose and plasma protein and to improve the growth performance of juvenile P. brachypomus during the growth-out phase. [Open Vet J 2024; 14(6.000): 1384-1393]

Abstract According to the latest cancer research data, there are a significant number of new cancer cases and a substantial mortality rate each year. Although a substantial number of clinical patients are treated with existing cancer drugs each year, the efficacy is unsatisfactory. The incidence is still high and the effectiveness of most cancer drugs remains unsatisfactory. Therefore, we evaluated the human proteins for their causal relationship to for cancer risk and therefore also their potential as drug targets. We used summary tumors data from the FinnGen and cis protein quantitative trait loci (cis-pQTL) data from a genome-wide association study, and employed Mendelian randomization (MR) to explore the association between potential drug targets and nine tumors, including breast, colorectal, lung, liver, bladder, prostate, kidney, head and neck, pancreatic caners. Furthermore, we conducted MR analysis on external cohort. Moreover, Bidirectional MR, Steiger filtering, and colocalization were employed to validate the main results. The DrugBank database was used to discover potential drugs of tumors. Under the threshold of False discovery rate (FDR)

Abstract 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.

Background: Previous epidemiological studies have identified a correlation between serum protein levels and Psoriatic Arthritis (PsA). However, the precise nature of this relationship remains uncertain. Therefore, our objective was to assess whether circulating levels of 2,923 plasma proteins are associated with the risk of PsA, utilizing the Mendelian randomization (MR) approach. Methods: Two-sample MR analysis was performed to assess the causal impact of proteins on PsA risk. Exposure data for plasma proteins were sourced from a genome-wide association study (GWAS) conducted within the UK Biobank Pharma Proteomics Project, which encompassed 2,923 unique plasma proteins. The outcome data for PsA were sourced from the FinnGen study, a large-scale genomics initiative, comprising 3,537 cases and 262,844 controls. Additionally, colocalization analysis, Phenome-wide MR analysis, and candidate drug prediction were employed to identify potential causal circulating proteins and novel drug targets. Results: We thoroughly assessed the association between 1,837 plasma proteins and PsA risk, identifying seven proteins associated with PsA risk. An inverse association of Interleukin-10 (IL-10) with PsA risk was observed [odds ratio (OR)=0.45, 95% confidence interval (CI), 0.28 to 0.70, PFDR=0.072]. Additionally, Apolipoprotein F (APOF) has a positive effect on PsA risk (OR=2.08, 95% CI, 1.51 to 2.86, PFDR=0.005). Subsequently, we found strong evidence indicating that IL-10 and APOF were colocalized with PsA associations (PP.H4 = 0.834 for IL-10 and PP.H4 = 0.900 for APOF). Phenome-wide association analysis suggested that these two proteins may have dual effects on other clinical traits (PFDR<0.1). Conclusion: This study identified 7 plasma proteins associated with PsA risk, particularly IL-10 and APOF, which offer new insights into its etiology. Further studies are needed to assess the utility and effectiveness of these candidate proteins. [ABSTRACT FROM AUTHOR]

Background: Proteome‐wide Mendelian randomization studies have been increasingly utilized to identify potential drug targets for diseases. We aimed to identify potential therapeutic targets for migraine and its subtypes through the application of Mendelian randomization and co‐localization analysis methods. Methods: We utilized cis‐protein quantitative trait loci data for 1378 plasma proteins available from two studies with 7213 individuals and 35,559 individuals, respectively. Summary data for migraine and its subtypes were obtained from a genetic study involving up to 1,339,303 individuals. Proteins that passed both the discovery and validation Mendelian randomization analysis, sensitivity analysis, heterogeneity test, and pleiotropy test, were associated with ≥2 outcomes, and received strong support from co‐localization analysis (PP.H4.abf ≥0.80) and were classified as tier 1 proteins. Results: We identified three tier 1 proteins (LRP11, ITIH1, and ADGRF5), whose genes have not been previously identified as causal genes for migraine in genetic studies. LRP11 was significantly associated with the risk of any migraine (OR [odds ratio] = 0.968, 95% CI [confidence interval] = 0.955–0.981, p = 1.27 × 10−6) and significantly/suggestively associated with three migraine subtypes. ITIH1 was significantly associated with the risk of any migraine (OR = 1.044, 95% CI = 1.024–1.065, p = 1.08 × 10−5) and migraine with visual disturbances. ADGRF5 was significantly associated with the risk of any migraine (OR = 0.964, 95% CI = 0.946–0.982, p = 8.74 × 10−5) and suggestively associated with migraine with aura. The effects of LRP11 and ADGRF5 were further replicated using cerebrospinal fluid protein data. Apart from ADGRF5, there was no evidence of potential adverse consequences when modulating the plasma levels. We also identified another four proteins (PLCG1, ARHGAP25, CHGA, and MANBA) with no potential adverse consequences when modulating the plasma levels, and their genes were not reported by previous genetic studies. Conclusions: We found compelling evidence for two proteins and suggestive evidence for four proteins that could be promising targets for migraine treatment without significant adverse consequences. The corresponding genes were not reported in previous genetic studies. Future studies are needed to confirm the causal role of these proteins and explore the underlying mechanisms. [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]

According to the latest cancer research data, there are a significant number of new cancer cases and a substantial mortality rate each year. Although a substantial number of clinical patients are treated with existing cancer drugs each year, the efficacy is unsatisfactory. The incidence is still high and the effectiveness of most cancer drugs remains unsatisfactory. Therefore, we evaluated the human proteins for their causal relationship to for cancer risk and therefore also their potential as drug targets. We used summary tumors data from the FinnGen and cis protein quantitative trait loci (cis-pQTL) data from a genome-wide association study, and employed Mendelian randomization (MR) to explore the association between potential drug targets and nine tumors, including breast, colorectal, lung, liver, bladder, prostate, kidney, head and neck, pancreatic caners. Furthermore, we conducted MR analysis on external cohort. Moreover, Bidirectional MR, Steiger filtering, and colocalization were employed to validate the main results. The DrugBank database was used to discover potential drugs of tumors. Under the threshold of False discovery rate (FDR) < 0.05, results showed that S100A16 was protective protein and S100A14 was risk protein for human epidermal growth factor receptor 2-positive (HER-positive) breast cancer, phosphodiesterase 5A (PDE5A) was risk protein for colorectal cancer, and melanoma inhibitory activity (MIA) was protective protein for non-small cell lung carcinoma (NSCLC). And there was no reverse causal association between them. Colocalization analysis showed that S100A14 (PP.H4.abf = 0.920) and S100A16 (PP.H4.abf = 0.932) shared causal variation with HER-positive breast cancer, and PDE5A (PP.H4.abf = 0.857) shared causal variation with colorectal cancer (CRC). The MR results of all pQTL of PDE5A and MIA were consistent with main results. In addition, the MR results of MIA and external outcome cohort were consistent with main results. In this study, genetic predictions indicate that circulating S100 calcium binding protein A14 (S100A14) and S100 calcium binding protein A16 (S100A16) are associated with increase and decrease in the risk of HER-positive breast cancer, respectively. Circulating PDE5A is associated with increased risk of CRC, while circulating MIA is associated with decreased risk of NSCLC. These findings suggest that four proteins may serve as biomarkers for cancer prevention and as potential drug targets that could be expected for approval. [ABSTRACT FROM AUTHOR]

Background: The currently available medications for treating membranous nephropathy (MN) still have unsatisfactory efficacy in inhibiting disease recurrence, slowing down its progression, and even halting the development of end-stage renal disease. There is still a need to develop novel drugs targeting MN. Methods: We utilized summary statistics of MN from the Kiryluk Lab and obtained plasma protein data from Zheng et al. We performed a Bidirectional Mendelian randomization analysis, HEIDI test, mediation analysis, Bayesian colocalization, phenotype scanning, drug bank analysis, and protein-protein interaction network. Results: The Mendelian randomization analysis uncovered 8 distinct proteins associated with MN after multiple false discovery rate corrections. Proteins related to an increased risk of MN in plasma include ABO [(Histo-Blood Group Abo System Transferase) (WR OR = 1.12, 95%CI:1.05-1.19, FDR=0.09, PPH4 = 0.79)], VWF [(Von Willebrand Factor) (WR OR = 1.41, 95%CI:1.16-1.72, FDR=0.02, PPH4 = 0.81)] and CD209 [(Cd209 Antigen) (WR OR = 1.19, 95%CI:1.07-1.31, FDR=0.09, PPH4 = 0.78)], and proteins that have a protective effect on MN: HRG [(Histidine-Rich Glycoprotein) (WR OR = 0.84, 95%CI:0.76-0.93, FDR=0.02, PPH4 = 0.80)], CD27 [(Cd27 Antigen) (WR OR = 0.78, 95%CI:0.68-0.90, FDR=0.02, PPH4 = 0.80)], LRPPRC [(Leucine-Rich Ppr Motif-Containing Protein, Mitochondrial) (WR OR = 0.79, 95%CI:0.69-0.91, FDR=0.09, PPH4 = 0.80)], TIMP4 [(Metalloproteinase Inhibitor 4) (WR OR = 0.67, 95%CI:0.53-0.84, FDR=0.09, PPH4 = 0.79)] and MAP2K4 [(Dual Specificity Mitogen-Activated Protein Kinase Kinase 4) (WR OR = 0.82, 95%CI:0.72-0.92, FDR=0.09, PPH4 = 0.80)]. ABO, HRG, and TIMP4 successfully passed the HEIDI test. None of these proteins exhibited a reverse causal relationship. Bayesian colocalization analysis provided evidence that all of them share variants with MN. We identified type 1 diabetes, trunk fat, and asthma as having intermediate effects in these pathways. Conclusions: Our comprehensive analysis indicates a causal effect of ABO, CD27, VWF, HRG, CD209, LRPPRC, MAP2K4, and TIMP4 at the genetically determined circulating levels on the risk of MN. These proteins can potentially be a promising therapeutic target for the treatment of MN. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study was to detect potential cytokines markers involved in the Graves’ orbitopathy (GO). Materials and Methods: We measured 25 plasma cytokines using label-free quantitative proteomic analysis in the pilot cohort. In validation cohort, NORCH3, TBP, α-enolase (ENO1), GPX3, ORM1, extracellular matrix protein-1 (ECM1), SERPINE, IGF1, IGKV1, and SPARC were validated using ELISA kits. We used label-free liquid chromatography–mass spectrometry/MS (LC–MS/MS) quantitative proteomic to analyze plasma cytokines content of Graves’ disease and GO patients. Results: The validation cohort showed that the concentrations of ECM1, ENO1, and GPX3, (244.4276 pg/ml, 4.361807 ng/ml, and 17.72794 pmol/ml, respectively) were significantly lower in GO patients samples than those in Graves’ patients (257.3197 pg/ml, 4.601592 ng/ml, and 21.33118 pmol/ml, respectively). Both univariate and multivariate logistic analyses indicated that GPX3, ECM1, and ENO might be predictors of Graves’ ophthalmopathy. A receiver-operating characteristic curve with an area under the curve of 0.938, a sensitivity of 84.4%, and a specificity of 90.5% underscored the applicability of this method. Conclusions: ECM1, ENO1, and GPX3 were associated with the presence of the GO group and may be good biomarkers that play an important role in the pathogenesis of GO.

Alzheimer's disease (AD) is suggested to be a heterogeneous disorder, but limited studies explore the heterogeneity of the Mild Cognitive Impairment (MCI) stage. This study aimed to tackle such problems using the CIMLR (Cancer Integration via Multikernel Learning) algorithm to cluster brain structural features extracted from T1-weighted Magnetic Resonance Images of MCI patients from Alzheimer's Disease Neuroimaging Initiative. The demographic and cognitive results, characteristics of brain structural features, plasma biomarkers, and longitudinal cognitive trajectory were analyzed for each cluster. The CIMLR clustering analysis revealed four distinct clusters. Cluster 1 is the oldest group but has had mild atrophy and moderate progression with elevated Tumor Necrosis Factor Receptor 2 level; and low Brain-Derived Neurotrophic Factor and CD40 Ligand levels. Cluster 2 showed the highest risk for aggressive MCI progression, with abnormal Leptin, Adiponectin, and Creatine kinase-MB values. Cluster 3 exhibited a low level of Monokine Induced by Gamma Interferon and mild atrophy that shared similar patterns with Cluster 1. Cluster 4 represented the healthiest group during longitudinal tracking, with the mildest Parahippocampal atrophy, which was found to be positively correlated with cognitive impairment and amino acid levels. The longitudinal analyses showed the potential of Hepatocyte Growth Factor as a marker for slow cognitive impairment; Cortisol and Neurofilament Light Polypeptide as prognosis markers for aggressive MCI progression. These findings may lay out new suggestions for further research contributing to the accurate diagnosis and precision medicine for dementia and AD.

Abstract Background We aim to examine the association between ultra-processed foods (UPF) consumption and cardiovascular disease (CVD) risk and to identify plasma proteins associated with UPF. Methods This prospective cohort study included 26,369 participants from the Swedish Malmö Diet and Cancer Study, established in 1991–1996. Dietary intake was assessed using a modified diet history method, and UPF consumption was estimated using the NOVA classification system. A total of 88 selected CVD-related proteins were measured among 4475 subjects. Incident CVD (coronary heart disease and ischemic stroke) was defined as a hospital admission or death through registers. Cox proportional hazards regression models were performed to analyze the associations of UPF intake with risks of CVD. Linear regression models were used to identify the plasma proteins associated with UPF intake. Results During 24.6 years of median follow-up, 6236 participants developed CVD, of whom 3566 developed coronary heart disease and 3272 developed ischemic stroke. The adjusted hazard ratio (95% confidence interval) in the 4th versus 1st quartile of UPF was 1.18 (1.08, 1.29) for CVD, 1.20 (1.07, 1.35) for coronary heart disease, and 1.17 (1.03, 1.32) for ischemic stroke. Plasma proteins interleukin 18, tumor necrosis factor receptor 2, macrophage colony-stimulating factor 1, thrombomodulin, tumor necrosis factor receptor 1, hepatocyte growth factor, stem cell factor, resistin, C–C motif chemokine 3, and endothelial cell-specific molecule 1 were positively associated with UPF after correcting for multiple testing. Conclusions Our study showed that high UPF intake increased the risk of CVD and was associated with several protein biomarkers. Future studies are warranted to validate these findings and assess the potential pathways between UPF intake and CVD.

Background: We aim to examine the association between ultra-processed foods (UPF) consumption and cardiovascular disease (CVD) risk and to identify plasma proteins associated with UPF. Methods: This prospective cohort study included 26,369 participants from the Swedish Malmö Diet and Cancer Study, established in 1991–1996. Dietary intake was assessed using a modified diet history method, and UPF consumption was estimated using the NOVA classification system. A total of 88 selected CVD-related proteins were measured among 4475 subjects. Incident CVD (coronary heart disease and ischemic stroke) was defined as a hospital admission or death through registers. Cox proportional hazards regression models were performed to analyze the associations of UPF intake with risks of CVD. Linear regression models were used to identify the plasma proteins associated with UPF intake. Results: During 24.6 years of median follow-up, 6236 participants developed CVD, of whom 3566 developed coronary heart disease and 3272 developed ischemic stroke. The adjusted hazard ratio (95% confidence interval) in the 4th versus 1st quartile of UPF was 1.18 (1.08, 1.29) for CVD, 1.20 (1.07, 1.35) for coronary heart disease, and 1.17 (1.03, 1.32) for ischemic stroke. Plasma proteins interleukin 18, tumor necrosis factor receptor 2, macrophage colony-stimulating factor 1, thrombomodulin, tumor necrosis factor receptor 1, hepatocyte growth factor, stem cell factor, resistin, C–C motif chemokine 3, and endothelial cell-specific molecule 1 were positively associated with UPF after correcting for multiple testing. Conclusions: Our study showed that high UPF intake increased the risk of CVD and was associated with several protein biomarkers. Future studies are warranted to validate these findings and assess the potential pathways between UPF intake and CVD. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the effect of pectin supplemented feeds on the growth, gut morphology and immunology of Labeo rohita. Experimental feeds containing various concentrations of pectin including control (0%), T1 (0.5%), T2 (1.0%), T3 (2.0%), and T4 (4.0%) were administered to L. rohita twice per day at a rate of 3% body weight. There was a significant (P < 0.05) decrease in average final weight, weight gain%, net weight gain and specific growth rate observed in treatment groups in order of control > T1 > T2 > T3 > T4 while feed conversion ratio was significantly (P < 0.05) higher in T4 compared to the other groups T3 > T2 > T1 > control. Immunological parameters of peroxidase, protease and antiprotease (trypsin) showed significant (P T2 > T1 > control group. Total protein, protease and antiprotease activity were significantly (P < 0.05) higher in the control compared to treatment groups T1 > T2 > T3 > T4. An increased level of the non-starch polysaccharide pectin in feed caused acute effects on gut morphometry. Villus length, villus width, and an increase in mucosal folds were abnormal but no significant (P > 0.05) abnormality was observed in the control group. In the submucosal part of the intestine, hyperplasia was shown in loose connective tissues and in adipose tissue cells in the treated groups. In conclusion, dietary pectin supplementation from 0.5% to 4% had negative effects on the growth, immunological parameters and gut histomorphology of L. rohita.

Context α2-Macroglobulin (α2-M) is believed to be a potential anti-irradiation agent, but related mechanisms remains unclear.Objective We investigated the irradiation protective effect of α2-M.Materials and methods A total of 10 Gy dose of irradiation was used to damage human skin fibroblasts. The influence of α2-M (100 µg/mL) on the proliferation, migration, invasion and apoptosis of fibroblasts was observed using Cell Counting Kit-8 (CCK8), wound healing, transwell, and flow cytometry. Malondialdehyde, superoxide dismutase and catalase was measured using related ELISA kits. The levels of mitochondrial membrane potential and calcium were detected using flow cytometry. The expression of transient receptor potential melastatin 2 (TRPM2) was investigated through western blotting and immunofluorescence staining.Results High purity of α2-M was isolated from Cohn fraction IV. α2-M significantly increased cell proliferation, migration, invasion, but suppressed cell apoptosis after irradiation. The promotion of cell proliferation, migration and invasion by α2-M exceeded over 50% compared group irradiation. The increased cell ratio in the S phase and decreased cell ratio in the G2 phase induced by irradiation were remarkably reversed by α2-M. α2-M markedly suppressed the increased oxidative stress level caused by irradiation. The mitochondrial damage induced by irradiation was improved by α2-M through inhibiting mitochondrial membrane potential loss, calcium and TRPM2 expression.Discussion and conclusions α2-M significantly promoted the decreased fibroblast viability and improved the mitochondria dysfunction caused by irradiation. α2-M might present anti-radiation effect through alleviating mitochondrial dysfunction caused by irradiation. This study could provide a novel understanding about the improvement of α2-M on irradiation-induced injury.

Simple Summary: The interactions between circulating tumor cells (CTCs) and plasma proteins are critical for hematogenous metastasis, and understanding the molecular mechanisms behind these interactions can improve liquid-biopsy-based diagnostics and cancer therapies. This review summarizes recent literature on the surface molecules of CTCs that interact with coagulation proteins and their biological and clinical relevance. It also discusses future research directions to expand our knowledge of the CTC interactome, which can lead to the discovery of new molecular markers for diagnostics and additional targets for cancer therapies. Cancer metastasis is a complex process. After their intravasation into the circulation, the cancer cells are exposed to a harsh environment of physical and biochemical hazards. Whether circulating tumor cells (CTCs) survive and escape from blood flow defines their ability to metastasize. CTCs sense their environment with surface-exposed receptors. The recognition of corresponding ligands, e.g., fibrinogen, by integrins can induce intracellular signaling processes driving CTCs' survival. Other receptors, such as tissue factor (TF), enable CTCs to induce coagulation. Cancer-associated thrombosis (CAT) is adversely connected to patients' outcome. However, cancer cells have also the ability to inhibit coagulation, e.g., through expressing thrombomodulin (TM) or heparan sulfate (HS), an activator of antithrombin (AT). To that extent, individual CTCs can interact with plasma proteins, and whether these interactions are connected to metastasis or clinical symptoms such as CAT is largely unknown. In the present review, we discuss the biological and clinical relevance of cancer-cell-expressed surface molecules and their interaction with plasma proteins. We aim to encourage future research to expand our knowledge of the CTC interactome, as this may not only yield new molecular markers improving liquid-biopsy-based diagnostics but also additional targets for better cancer therapies. [ABSTRACT FROM AUTHOR]

Background Finding effective and safe therapeutic drugs for atrial fibrillation (AF) is an important concern for clinicians. Proteome‐wide Mendelian randomization analysis provides new ideas for finding potential drug targets. Methods and Results Using a proteome‐wide Mendelian randomization approach, we assessed the genetic predictive causality between thousands of proteins and AF risk and found that genetically predicted plasma levels of phosphomevalonate kinase, tumor necrosis factor ligand superfamily member 12, sulfhydryl oxidase 2, interleukin‐6 receptor subunit alpha, and low‐affinity immunoglobulin gamma Fc region receptor II‐b might decrease AF risk, while genetically predicted plasma levels of beta‐mannosidase, collagen alpha‐1(XV) chain, ANXA4 (annexin A4), COF2 (cofilin‐2), and RAB1A (Ras‐related protein Rab‐1A) might increase AF risk (P

Freshwater turtles are sensitive to environmental changes and can serve as sentinel species for ecosystem health assessments. The Efroymson Restoration at Kankakee Sands in northwestern Indiana, USA has been restored in the past 25 yr from primarily agricultural land to a mosaic of prairie and wetland habitats. Health assessments of 40 free-ranging painted turtles (Chrysemys picta) at Kankakee Sands were performed in May 2021 to evaluate overall health status, screen for infectious diseases, and obtain baseline clinical pathology values in this population. Assessment of each turtle included a physical examination, complete blood count, plasma biochemistry panel, blood lactate level, venous blood gas analysis, serum trace mineral panel, serum vitamin D3 level, and plasma protein electrophoresis. Oral and cloacal swabs were tested for adenoviruses, herpesviruses, frog virus 3, and Mycoplasmopsis species by PCR in 39 painted turtles. Four turtles were positive for adenovirus, which shared 100% homology to Sulawesi tortoise adenovirus. Two turtles were herpesvirus-positive with 100% homology to emydid herpesvirus 1. No Mycoplasmopsis spp. or frog virus 3 was detected. Female turtles had significantly higher manganese, prealbumin, uric acid, triglycerides, and ionized calcium levels, while male turtles had significantly higher cholesterol, glutamate dehydrogenase, and CO2 levels. These baseline data can be used for future research into freshwater turtle health in restored wetland habitats. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the effect of pectin supplemented feeds on the growth, gut morphology and immunology of Labeo rohita. Experimental feeds containing various concentrations of pectin including control (0%), T1 (0.5%), T2 (1.0%), T3 (2.0%), and T4 (4.0%) were administered to L. rohita twice per day at a rate of 3% body weight. There was a significant (P < 0.05) decrease in average final weight, weight gain%, net weight gain and specific growth rate observed in treatment groups in order of control > T1 > T2 > T3 > T4 while feed conversion ratio was significantly (P < 0.05) higher in T4 compared to the other groups T3 > T2 > T1 > control. Immunological parameters of peroxidase, protease and antiprotease (trypsin) showed significant (P < 0.05) results between control and treated groups. Peroxidase activity was significantly (P < 0.05) higher in T4 group fish compared to T3 > T2 > T1 > control group. Total protein, protease and antiprotease activity were significantly (P < 0.05) higher in the control compared to treatment groups T1 > T2 > T3 > T4. An increased level of the nonstarch polysaccharide pectin in feed caused acute effects on gut morphometry. Villus length, villus width, and an increase in mucosal folds were abnormal but no significant (P > 0.05) abnormality was observed in the control group. In the submucosal part of the intestine, hyperplasia was shown in loose connective tissues and in adipose tissue cells in the treated groups. In conclusion, dietary pectin supplementation from 0.5% to 4% had negative effects on the growth, immunological parameters and gut histomorphology of L. rohita. [ABSTRACT FROM AUTHOR]

Abstract Understanding material‐protein interactions is the basis for regulating material‐blood interactions, which is a common topic of interest for medical material developers. In recent years, researchers have conducted extensive studies on (1) the structural characteristics of the plasma protein adsorption layer on the material surface, including the evolution of the protein adsorption layer and its typical binary structure. (2) Influence factors of the protein adsorption layer formation include protein factors (e.g., isoelectric point, structural stability), material factors (e.g., wettability, surface charge, morphology, size), and environmental factors. (3) Effects of some common plasma proteins in the protein adsorption layer on material‐blood interactions. Here, we review the important research results in this field, hoping to provide a reference for future development of advanced blood contact materials.

Aims The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA). Methods Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls. Results We found that seven kinds of plasma proteins had genetic correlations with RA, such as Soluble Receptor for Advanced Glycation End Products (sRAGE) (correlation coefficient = 0.2582, p = 0.049), vesicle transport protein USE1 (correlation coefficient = 0.1337, p = 0.018), and spermatogenesis-associated protein 20 (correlation coefficient = 0.3706, p = 0.018). There was a significant causal relationship between sRAGE and RA. By comparing the genes encoding seven plasma proteins, we found that only USE1 was a DEG associated with RA. Conclusion Our study identified a set of candidate plasma proteins that showed signals correlated with RA. Since the results of this study need further experimental verification, they should be interpreted with caution. However, we hope that this paper will provide new insights for the discovery of pathogenic genes and RA pathogenesis in the future. Cite this article: Bone Joint Res 2022;11(2):134–142.

Background and aimsPrimary biliary cholangitis (PBC) is a progressive chronic autoimmune cholestatic liver disease characterized by the destruction of small intrahepatic bile ducts leading to biliary cirrhosis. Liver biopsy is required in the diagnosis of Antimitochondrial antibody-negative patients. Therefore, novel biomarkers are needed for the non-invasive diagnosis of PBC. To identify novel biomarkers for PBC, we conducted large-scale plasma proteome Mendelian randomization (MR).MethodsA total of 21,593 protein quantitative trait loci (pQTLs) for 2297 circulating proteins were used and classified into four different groups. MR analyses were conducted in the four groups separately. Furthermore, the results were discovered and replicated in two different cohorts of PBC. Colocalization analysis and enrichment analysis were also conducted.ResultsThree plasma proteins (ficolin-1, CD40 and protein FAM177A1) were identified and replicated as being associated with PBC. All of them showed significant protective effects against PBC. An increase in ficolin-1 (OR=0.890 [0.843-0.941], p=3.50×10-5), CD40 (OR=0.814 [0.741-0.895], p=1.96×10-5) and protein FAM177A1 (OR=0.822 [0.754-0.897], p=9.75×10-6) reduced the incidence of PBC. Ficolin-1 (PP4 = 0.994) and protein FAM177A1 (PP4 = 0.995) colocalized with the expression of the genes FCN1 and FAM177A1 in whole blood, respectively. Furthermore, CD40 (PP4 = 0.977) and protein FAM177A1 (PP4 = 0.897) strongly colocalized with PBC.ConclusionsWe expand the current biomarkers for PBC. In total, three (ficolin-1, CD40, and protein FAM177A1) plasma proteins were identified and replicated as being associated with PBC in MR analysis. All of them showed significant protective effects against PBC. These proteins can be potential biomarkers or drug targets for PBC.

Context: a2-Macroglobulin (a2-M) is believed to be a potential anti-irradiation agent, but related mechanisms remains unclear. Objective: We investigated the irradiation protective effect of a2-M. Objective: We investigated the irradiation protective effect of a2-M. Materials and methods: A total of 10 Gy dose of irradiation was used to damage human skin fibroblasts. The influence of a2-M (100 mg/mL) on the proliferation, migration, invasion and apoptosis of fibroblasts was observed using Cell Counting Kit-8 (CCK8), wound healing, transwell, and flow cytometry. Malondialdehyde, superoxide dismutase and catalase was measured using related ELISA kits. The levels of mitochondrial membrane potential and calcium were detected using flow cytometry. The expression of transient receptor potential melastatin 2 (TRPM2) was investigated through western blotting and immunofluorescence staining. Results: High purity of a2-M was isolated from Cohn fraction IV. a2-M significantly increased cell proliferation, migration, invasion, but suppressed cell apoptosis after irradiation. The promotion of cell proliferation, migration and invasion by a2-M exceeded over 50% compared group irradiation. The increased cell ratio in the S phase and decreased cell ratio in the G2 phase induced by irradiation were remarkably reversed by a2-M. a2-M markedly suppressed the increased oxidative stress level caused by irradiation. The mitochondrial damage induced by irradiation was improved by a2-M through inhibiting mitochondrial membrane potential loss, calcium and TRPM2 expression. Discussion and conclusions: a2-M significantly promoted the decreased fibroblast viability and improved the mitochondria dysfunction caused by irradiation. a2-M might present anti-radiation effect through alleviating mitochondrial dysfunction caused by irradiation. This study could provide a novel understanding about the improvement of a2-M on irradiation-induced injury. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effects of spray-dried porcine plasma protein (SDPP) or spray-dried chicken plasma protein (SDCP) supplementation in diets without the inclusion of antibiotics and zinc oxide (ZnO) on growth performance, fecal score, and fecal microbiota in early-weaned piglets. A total of 192 healthy weaning piglets (Duroc × Landrace × Yorkshire, 21 d old) were blocked by BW (6.53 ± 0.60 kg) and randomly assigned to 4 dietary treatments: negative control (NC, basal diet), positive control (PC), basal diet + ZnO at 2 g/kg and antibiotics at 0.8 g/kg), SDPP (containing 5% SDPP), and SDCP (containing 5% SDCP). The experiment lasted 14 d. The SDPP group had higher (P

Patients at a high risk for sudden cardiac death (SCD) without previous history of cardiovascular disease remain a challenge to identify. Atherosclerosis and prothrombotic states involve inflammation and non-cardiac tissue damage that may play active roles in SCD development. Therefore, we hypothesized that circulating proteins implicated in inflammation and tissue damage are linked to the future risk of SCD. We conducted a prospective nested case–control study of SCD cases with verified myocardial infarction (N = 224) and matched controls without myocardial infarction (N = 224), aged 60 ± 10 years time and median time to event was 8 years. Protein concentrations (N = 122) were measured using a proximity extension immunoassay. The analyses revealed 14 proteins significantly associated with an increased risk of SCD, from which two remained significant after adjusting for smoking status, systolic blood pressure, BMI, cholesterol, and glucose levels. We identified leukotriene A4 hydrolase (LTA4H, odds ratio 1.80, corrected confidence interval (CIcorr) 1.02–3.17) and hepatocyte growth factor (HGF; odds ratio 1.81, CIcorr 1.06–3.11) as independent risk markers of SCD. Elevated LTA4H may reflect increased systemic and pulmonary neutrophilic inflammatory processes that can contribute to atherosclerotic plaque instability. Increased HGF levels are linked to obesity-related metabolic disturbances that are more prevalent in SCD cases than the controls. [ABSTRACT FROM AUTHOR]

Harsh work environments can include very cold, hot, dusty, and noisy workplaces, as well as exposure in the workplace with chemicals and other fumes, cigarette smoke, and diesel exhaust. Although working in these harsh environments can have a negative effect on health, there are no effective biomarkers for monitoring health conditions until workers develop disease symptoms. Plasma protein concentrations, which reflect metabolism and immune status, have great potential as biomarkers for various health conditions. Using a Mendelian-randomization (MR) design, this study analyzed the effects of these harsh environments on plasma proteins to identify proteins that can be used as biomarkers of health status. Preliminary analysis using inverse variance weighted (IVW) method with a p-value cutoff of 0.05 showed that workplace environments could affect the concentrations of hundreds of plasma proteins. After filtering for sensitivity via MR-Egger, and Weighted Median MR approaches, 28 plasma proteins altered by workplace environments were identified. Further MR analysis showed that 20 of these plasma proteins, including UNC5D, IGFBP1, SCG3, ST3GAL6, and ST3GAL2 are affected by noisy workplace environments; TFF1, RBM39, ACYP2, STAT3, GRB2, CXCL1, EIF1AD, CSNK1G2, and CRKL that are affected by chemical fumes; ADCYAP1, NRSN1, TMEM132A, and CA10 that are affected by passive smoking; LILRB2, and TENM4 that are affected by diesel exhaust, are associated with the risk of at least one disease. These proteins have the potential to serve as biomarkers to monitor the occupational hazards risk of workers working in corresponding environments. These findings also provide clues to study the biological mechanisms of occupational hazards.

Understanding material‐protein interactions is the basis for regulating material‐blood interactions, which is a common topic of interest for medical material developers. In recent years, researchers have conducted extensive studies on (1) the structural characteristics of the plasma protein adsorption layer on the material surface, including the evolution of the protein adsorption layer and its typical binary structure. (2) Influence factors of the protein adsorption layer formation include protein factors (e.g., isoelectric point, structural stability), material factors (e.g., wettability, surface charge, morphology, size), and environmental factors. (3) Effects of some common plasma proteins in the protein adsorption layer on material‐blood interactions. Here, we review the important research results in this field, hoping to provide a reference for future development of advanced blood contact materials. [ABSTRACT FROM AUTHOR]

Three experiments were conducted to determine phosphorus (P) digestibility and bioavailability using different methods. The objective of the first experiment was to determine ileal P digestibility of soybean meal (SBM), meat and bone meal (MBM), and spray-dried plasma protein (SDPP) using a precision-fed broiler chick assay. This assay involved feeding 8 g of SBM, MBM, or SDPP to broiler chicks at 21 D of age. At 6 h after feeding, ileal digesta were collected. Ileal P digestibility of SBM, MBM, and SDPP was 64, 42, and 94%, respectively. In the second experiment, ileal P digestibility and excreta P retention of SBM, SDPP, and MBM were determined using an ad libitum fed chick assay. On day 17 of age, chicks were placed on 1 of 12 dietary treatments that consisted of diets containing increasing levels of SBM, SDPP, or MBM. On day 21, ileal digesta and excreta were collected. True ileal P digestibility and true excreta P retention estimated using regression of ileal P or excreta P output on dietary P content yielded true ileal P digestibility values for SBM, SDPP, and MBM (2 diet methods for MBM) to be 83, 98, 61, and 23%, respectively. True excreta P retention values for SBM, SDPP, and MBM (2 methods) were determined to be 51, 99, 32, and 53%, respectively. The third experiment determined bioavailability of P in SBM, SDPP, and MBM relative to KH2PO4 using a chick bone ash bioassay. Dietary treatments included a P-deficient cornstarch–dextrose–SBM diet supplemented with 2 increasing levels of P from KH2PO4, SBM, SDPP, or MBM. Bioavailability of P based on tibia ash estimated using the multiple regression slope ratio method was 36, 125, and 76% for SBM, SDPP, and MBM, respectively, relative to KH2PO4. The results of this study indicated the digestibility/relative bioavailability of the P in SDPP was very high for all 3 methods, but values for SBM and MBM varied greatly among different methods.

Abstract A State of the Art lecture titled “Proteomics in Thrombosis Research” was presented at the ISTH Congress in 2021. In clinical practice, there is a need for improved plasma biomarker‐based tools for diagnosis and risk prediction of venous thromboembolism (VTE). Analysis of blood, to identify plasma proteins with potential utility for such tools, could enable an individualized approach to treatment and prevention. Technological advances to study the plasma proteome on a large scale allows broad screening for the identification of novel plasma biomarkers, both by targeted and nontargeted proteomics methods. However, assay limitations need to be considered when interpreting results, with orthogonal validation required before conclusions are drawn. Here, we review and provide perspectives on the application of affinity‐ and mass spectrometry‐based methods for the identification and analysis of plasma protein biomarkers, with potential application in the field of VTE. We also provide a future perspective on discovery strategies and emerging technologies for targeted proteomics in thrombosis research. Finally, we summarize relevant new data on this topic, presented during the 2021 ISTH Congress.

As early detection is crucial for improvement of cancer prognosis, we searched for biomarkers in plasma from individuals who later developed squamous cell carcinoma of the oral tongue (SCCOT) as well as in patients with an already established SCCOT. Levels of 261 proteins related to inflammation and/or tumor processes were measured using the proximity extension assay (PEA) in 179 plasma samples (42 collected before diagnosis of SCCOT with 81 matched controls; 28 collected at diagnosis of SCCOT with 28 matched controls). Statistical modeling tools principal component analysis (PCA) and orthogonal partial least square - discriminant analysis (OPLS-DA) were applied to provide insights into separations between groups. PCA models failed to achieve group separation of SCCOT patients from controls based on protein levels in samples taken prior to diagnosis or at the time of diagnosis. For pre-diagnostic samples and their controls, no significant OPLS-DA model was identified. Potentials for separating pre-diagnostic samples collected up to five years before diagnosis (n = 15) from matched controls (n = 28) were seen in four proteins. For diagnostic samples and controls, the OPLS-DA model indicated that 21 proteins were important for group separation. TNF receptor associated factor 2 (TRAF2), decreased in pre-diagnostic plasma (< 5 years) but increased at diagnosis, was the only protein showing altered levels before and at diagnosis of SCCOT (p -value < 0.05). Taken together, changes in plasma protein profiles at diagnosis were evident, but not reliably detectable in pre-diagnostic samples taken before clinical signs of tumor development. Variation in protein levels during cancer development poses a challenge for the identification of biomarkers that could predict SCCOT development. [ABSTRACT FROM AUTHOR]

Aim. The purpose of this study was to characterize the Propoxazepam properties of binding to the human, dog and rat plasma proteins and to evaluate potential interspecies differences in binding affinity. Methods. The studies on Plasma protein binding were conducted using the Rapid Equilibrium Dialysis system with subsequent LC MS/MS analysis. The albumin binding of the substances was characterized by the percentage of bound drug. Results. Propoxazepam was highly bound to the plasma proteins in rats, dogs and humans. The extent of Propoxazepam binding in human plasma was similar to that observed in rat plasma whereas it was slightly lower in dog plasma, following dialysis for 8 hours. Conclusions. No concentration dependent effects on plasma protein binding were observed in the species investigated for Propoxazepam. Overall mean free fractions of Propoxazepam were 1.60 %, 2.90 % and 1.96 % in rats, dogs and humans, respectively. The results obtained in this work gave insights on the role of HSA in distributing Propoxazepam to target tissues and in determining their pharmacological properties. The results are crucial for the development of Benzodizepines-based therapeutics drugs. [ABSTRACT FROM AUTHOR]

As early detection is crucial for improvement of cancer prognosis, we searched for biomarkers in plasma from individuals who later developed squamous cell carcinoma of the oral tongue (SCCOT) as well as in patients with an already established SCCOT. Levels of 261 proteins related to inflammation and/or tumor processes were measured using the proximity extension assay (PEA) in 179 plasma samples (42 collected before diagnosis of SCCOT with 81 matched controls; 28 collected at diagnosis of SCCOT with 28 matched controls). Statistical modeling tools principal component analysis (PCA) and orthogonal partial least square - discriminant analysis (OPLS-DA) were applied to provide insights into separations between groups. PCA models failed to achieve group separation of SCCOT patients from controls based on protein levels in samples taken prior to diagnosis or at the time of diagnosis. For pre-diagnostic samples and their controls, no significant OPLS-DA model was identified. Potentials for separating pre-diagnostic samples collected up to five years before diagnosis (n = 15) from matched controls (n = 28) were seen in four proteins. For diagnostic samples and controls, the OPLS-DA model indicated that 21 proteins were important for group separation. TNF receptor associated factor 2 (TRAF2), decreased in pre-diagnostic plasma (< 5 years) but increased at diagnosis, was the only protein showing altered levels before and at diagnosis of SCCOT (p-value < 0.05). Taken together, changes in plasma protein profiles at diagnosis were evident, but not reliably detectable in pre-diagnostic samples taken before clinical signs of tumor development. Variation in protein levels during cancer development poses a challenge for the identification of biomarkers that could predict SCCOT development.

Background: Alcohol consumption and cardiovascular disease (CVD) have a complex relation.Objectives: We examined the associations between alcohol consumption, fasting plasma proteins, and CVD risk.Methods: We performed cross-sectional association analyses of alcohol consumption with 71 CVD-related plasma proteins, and also performed prospective association analyses of alcohol consumption and protein concentrations with 3 CVD risk factors (obesity, hypertension, and diabetes) in 6745 Framingham Heart Study (FHS) participants (mean age 49 y; 53% women).Results: A unit increase in log10 transformed alcohol consumption (g/d) was associated with an increased risk of hypertension (HR = 1.14; 95% CI: 1.04, 1.26; P = 0.007), and decreased risks of obesity (HR = 0.80; 95% CI: 0.71, 0.91; P = 4.6 × 10-4) and diabetes (HR: 0.68; 95% CI: 0.58, 0.80; P = 5.1 × 10-6) in a median of 13-y (interquartile = 7, 14) of follow-up. We identified 43 alcohol-associated proteins in a discovery sample (n = 4348, false discovery rate <0.05) and 20 of them were significant (P <0.05/43) in an independent validation sample (n = 2397). Eighteen of the 20 proteins were inversely associated with alcohol consumption. Four of the 20 proteins demonstrated 3-way associations, as expected, with alcohol consumption and CVD risk factors. For example, a greater concentration of APOA1 was associated with higher alcohol consumption (P = 1.2 × 10-65), and it was also associated with a lower risk of diabetes (P = 8.5 × 10-6). However, several others showed unexpected 3-way associations.Conclusions: We identified 20 alcohol-associated proteins in 6745 FHS samples. These alcohol-associated proteins demonstrated complex relations with the 3 CVD risk factors. Future studies with integration of more proteomic markers and larger sample size are warranted to unravel the complex relation between alcohol consumption and CVD risk. [ABSTRACT FROM AUTHOR]

BackgroundThe liver-derived plasma protein fetuin A is a systemic inhibitor of ectopic calcification. Fetuin-A stabilizes calcium phosphate mineral initially as ion clusters to form calciprotein monomers (CPM), and then as larger multimeric consolidations containing amorphous calcium phosphate (primary CPP, CPP 1) or more crystalline phases (secondary CPP, CPP 2). CPM and CPP mediate excess mineral stabilization, transport and clearance from circulation.MethodsWe injected i.v. synthetic fluorescent CPM and studied their clearance by live two-photon microscopy. We analyzed organ sections by fluorescence microscopy to assess CPM distribution. We studied cellular clearance and cytotoxicity by flow cytometry and live/dead staining, respectively, in cultured macrophages, liver sinusoidal endothelial cells (LSEC), and human proximal tubule epithelial HK-2 cells. Inflammasome activation was scored in macrophages. Fetuin A monomer and CPM charge were analyzed by ion exchange chromatography.ResultsLive mice cleared CPP in the liver as published previously. In contrast, CPM were filtered by kidney glomeruli into the Bowman space and the proximal tubules, suggesting tubular excretion of CPM-bound calcium phosphate and reabsorption of fetuin A. Fetuin-A monomer clearance was negligible in liver and low in kidney. Anion exchange chromatography revealed that fetuin A monomer was negatively charged, whereas CPM appeared neutral, suggesting electrochemical selectivity of CPM versus fetuin A. CPM were non-toxic in any of the investigated cell types, whereas CPP 1 were cytotoxic. Unlike CPP, CPM also did not activate the inflammasome.ConclusionsFetuin-A prevents calcium phosphate precipitation by forming CPM, which transform into CPP. Unlike CPP, CPM do not trigger inflammation. CPM are readily cleared in the kidneys, suggesting CPM as a physiological transporter of excess calcium and phosphate. Upon prolonged circulation, e.g., in chronic kidney disease, CPM will coalesce and form CPP, which cannot be cleared by the kidney, but will be endocytosed by liver sinusoidal endothelial cells and macrophages. Large amounts of CPP trigger inflammation. Chronic CPM and CPP clearance deficiency thus cause calcification by CPP deposition in blood vessels and soft tissues, as well as inflammation.

Long-term exposures to low-dose radiation (LDR) may trigger several specific biological responses, including dysregulation of the immune and inflammatory systems. Here, we examined whether biodosimetry of LDR can be used to protect tissues from radiation or assess cancer risk. Mice were subjected to gamma-irradiation with repeated or single-dose LDR, and then the organ indices, peripheral hemogram, and blood biochemistry were analyzed. An antibody array was applied followed by enzyme-linked immunosorbent assay to evaluate the utility of multiple plasma proteins as biomarkers of repeated LDR in a murine model. LDR induced inapparent symptoms but slight variations in peripheral blood cell counts and alterations in blood biochemical indicator levels. Specific plasma proteins in the LDR groups were altered in response to a higher dose of irradiation at the same time points or a single-dose equivalent to the same total dose. Plasma levels of interleukin (IL)-5, IL-12p40, P-selectin, and serum amyloid A1 were associated with the LDR dose and thus may be useful as dosimetric predictors of LDR in mice. Estimating the levels of certain plasma proteins may yield promising biodosimetry parameters to accurately identify individuals exposed to LDR, facilitating risk assessment of long-term LDR exposure in individuals. [ABSTRACT FROM AUTHOR]

Whey proteins are a primary component of milk replacers (MR) and are considered the gold standard for calves. Alternative protein sources may decrease MR cost if calf performance is similar. A blend of bovine plasma protein and modified wheat protein might be a good partial replacement for whey protein. Usually MR is fed twice daily, but feeding 3 times daily might increase efficiency of nutrient use, especially with MR containing alternate proteins. Therefore, our objective was to determine the effects of 2 MR, containing either entirely whey protein (CON) or a combination of whey protein, bovine plasma protein, and modified wheat protein (WBP), when fed in either 2 or 3 meals daily on calf growth and health. Female and male Holstein calves (n = 103) housed in individual hutches were studied for the first 63 d of life, with additional measurements obtained at wk 12 of life in group housing. The MR contained 25% CP, 17% fat, and a Lys:Met ratio of 3.1:1. Individual treatments arose from the 2 × 2 factorial arrangement of MR formulation and frequency of feeding. After colostrum, calves were fed MR (12.5% solids) at daily rates of dry matter dependent on age. Amounts were as follows: d 3 to 10 = 0.52 kg/d (2× = 0.259 kg, 3× = 0.173 kg per feeding); d 11 to 20 = 0.68 kg/d (2× = 0.341 kg, 3× = 0.227 kg per feeding); d 21 to 42 = 0.84 kg/d (2× = 0.42 kg, 3× = 0.28 kg per feeding); d 43 to 46, 47, 49, and 51 = 0.42 kg/d, with both 2× and 3× changed to 1 feeding daily and skip days (d 48 and 50) between where calves were not given MR; and d 52 = calves weaned. Starter was fed and intake was measured from d 1 until d 63. Intakes, health scores, attitude scores, and fecal scores were measured daily. Body weight (BW) and growth measurements were obtained weekly until wk 8 and again at wk 12. Blood samples were obtained at 0, 24, and 48 h and then on d 5, 14, 28, and 42 of age. Starter intake was greater for calves fed WBP versus CON during wk 7 to 9. Final BW and hip width at wk 12 were greater for calves fed WBP than for calves fed CON. Calves fed 2× had greater mean and final BW to wk 6 and greater feed efficiency (gain:feed ratio) than calves fed 3×. Blood variables supported the generally similar growth outcomes. Health outcomes did not differ between diets or feeding frequencies. Overall, calves fed WBP had increased starter intake and greater BW gains during wk 7 to 12 than calves fed CON, and calves fed 2× had increased growth and feed efficiency compared with those fed 3×. [ABSTRACT FROM AUTHOR]