Dataset supporting paper ‘Acute effects of an anthocyanin-rich blackcurrant beverage on markers of cardiovascular disease risk in healthy adults: a randomized, double-blind, placebo-controlled, crossover trial’

This dataset includes all summaries of raw data supporting the results presented in the paper "Acute effects of an anthocyanin-rich blackcurrant beverage on markers of cardiovascular disease risk in healthy adults: a randomized, double-blind, placebo-controlled, crossover trial". The objective of this paper is to investigate the postprandial effects of an anthocyanin-rich blackcurrant beverage (200 mL containing 711 mg anthocyanins) on a range of CVD risk markers in a healthy, middle-aged population. Data about CVD risk markers include: i. flow-mediated dilation (FMD) measured by Phillips CX50 integrated ultrasound system; ii. digital volume pulse (DVP) measured by PulseTrace PCA 2 device with finger photoplethysmography; iii. Blood pressure (BP) measured by by an automated sphygmomanometer; iv. platelet aggregation induced with two agonists: collagen (0.5 and 1 µg/mL final concentration) and ADP (10 and 100 µM final concentration) measured by chronolog optical platelet aggregometer; v. interleukin-8 (IL-8) concentrations measured by enhanced sensitivity cytometric bead array kit; vi. platelet-derived extracellular vesicles (PDEVs) and endothelium-derived extracellular vesicles (EDEVs) concentrations measured by flow cytometer. Data about plasma and urine anthocyanin and phenolic metabolites concentrations were measured by UPLC-MS/MS

Dataset supporting paper 'Dietary n-3 polyunsaturated fatty acids alter the number, fatty acid profile and coagulatory activity of circulating and platelet-derived extracellular vesicles'

This dataset includes all reports and summaries of raw data supporting the results presented in the paper "Dietary n-3 polyunsaturated fatty acids alter the number, fatty acid profile and coagulatory activity of circulating and platelet-derived extracellular vesicles". The objective of this paper is to investigate whether daily supplementation of participants at moderate risk of (cardiovascular diseases) CVDs with 1.8 g/d of fish oil-derived n-3 polyunsaturated fatty acids (PUFAs) altered the generation, composition and function of circulating and platelet-derived extracellular vesicles (EVs). Data about EVs parameters include: i. the numbers, and size of circulating total EVs and in vitro generated platelet-derived EVs (PDEVs) measured by Nanoparticle Tracking Analysis (NTA); ii. the numbers of EV subpopulations (i.e. phosphatidylserine-positive EVs (PS+EVs), PDEVs, endothelial-derived EVs (EDEVs)) and PS expression on PDEVs generated in vitro from platelets measured by flow cytometry (FCM); iii. the procoagulatory activity of circulating EVs (in vitro thrombogenic potential in activating tissue factor-dependent thrombin generation) measured by thrombin generation assay. The coagulatory behaviour of PDEVs generated in vitro from platelets measured by thrombin generation, clot formation, fibrinolysis and in vivo thrombus formation assays. Data about conventional cardiovascular risk markers include i. body mass index (BMI) measured by Tanita; ii. blood pressure measured by upper arm blood pressure monitor; iii. plasma lipid profile (i.e. triacylglycerol (TAG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and glucose concentrations measured by iLab. Data about thrombogenic markers include: i. plasma platelet aggregation measured by 96-well high-throughput aggregometry; ii. plasma thrombin generation measured by thrombin generation assay; iii. plasma clot growth and fibrinolysis measured by thrombodynamics analyzer

Dataset supporting paper ‘Fish oil supplements, but not oily fish, alter the number and function of extracellular vesicles in healthy human subjects: A randomized, double-blind, placebo-controlled, parallel trial’

This dataset includes all summaries of raw data supporting the results presented in the paper "Fish oil supplements, but not oily fish, alter the number and function of extracellular vesicles in healthy human subjects: A randomized, double-blind, placebo-controlled, parallel trial".The objective of this paper is to investigate the effects of fish oil supplements providing 2.2 g/d of n-3 polyunsaturated fatty acids (PUFAs) and oily fish at a level achievable in the diet providing 1.44 g/d of n-3 PUFA, on the numbers, compositions and procoagulant activity of extracellular vesicles (EVs) in healthy human volunteers. Data about EVs parameters include: i. the numbers, and size of circulating total EVs measured by Nanoparticle Tracking Analysis (NTA); ii. the numbers of EV subpopulations (i.e. phosphatidylserine-positive EVs (PS+EVs), platelet-derived EVs (PDEVs), endothelial-derived EVs (EDEVs)) by flow cytometry (FCM); iii. the procoagulatory activity of circulating EVs including in vitro thrombogenic potential of EVs in activating tissue factor-dependent thrombin generation measured by thrombin generation assay and in vitro clot-forming capacity of EVs measured by clot formation and lysis assays. Data about fatty acid compositions of red blood cells (RBCs) and EVs were measured by gas chromatography. Data about plasma lipid profile include total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triacylglycerol concentrations measured by Randox. Data about subjects baseline characteristics include i. height, weight and body mass index (BMI) measured by Tanita; ii. blood pressure measured by upper arm blood pressure monitor

Systematic Investigation of the Homology Sequences Around the Human Fusion Gene Breakpoints in Pan-Cancer - Bioinformatics Study for a Potential Link to MMEJ

Microhomology-mediated end joining (MMEJ), an error-prone DNA damage repair mechanism, frequently leads to chromosomal rearrangements due to its ability to engage in promiscuous end joining of genomic instability and also leads to increasing mutational load at the sequences flanking the breakpoints (BPs). In this study, we systematically investigated the homology sequences around the genomic breakpoint area of human fusion genes, which were formed by the chromosomal rearrangements initiated by DNA double-strand breakage. Since the RNA-seq data is the typical data set to check the fusion genes, for the known exon junction fusion breakpoints identified from RNA-seq data, we have to infer the high chance of genomic breakpoint regions. For this, we utilized the high feature importance score area calculated from our recently developed fusion BP prediction model, FusionAI and identified 151 K microhomologies among ~24 K fusion BPs in 20 K fusion genes. From our multiple bioinformatics studies, we found a relationship between sequence homologies and the immune system. This in-silico study will provide novel knowledge on the sequence homologies around the coded structural variants

FusionNeoAntigen: A Resource of Fusion Gene-Specific Neoantigens

Among the diverse sources of neoantigens (i.e. single-nucleotide variants (SNVs), insertions or deletions (Indels) and fusion genes), fusion gene-derived neoantigens are generally more immunogenic, have multiple targets per mutation and are more widely distributed across various cancer types. Therefore, fusion gene-derived neoantigens are a potential source of highly immunogenic neoantigens and hold great promise for cancer immunotherapy. However, the lack of fusion protein sequence resources and knowledge prevents this application. We introduce \u27FusionNeoAntigen\u27, a dedicated resource for fusion-specific neoantigens, accessible at https://compbio.uth.edu/FusionNeoAntigen. In this resource, we provide fusion gene breakpoint crossing neoantigens focused on ∼43K fusion proteins of ∼16K in-frame fusion genes from FusionGDB2.0. FusionNeoAntigen provides fusion gene information, corresponding fusion protein sequences, fusion breakpoint peptide sequences, fusion gene-derived neoantigen prediction, virtual screening between fusion breakpoint peptides having potential fusion neoantigens and human leucocyte antigens (HLAs), fusion breakpoint RNA/protein sequences for developing vaccines, information on samples with fusion-specific neoantigen, potential CAR-T targetable cell-surface fusion proteins and literature curation. FusionNeoAntigen will help to develop fusion gene-based immunotherapies. We will report all potential fusion-specific neoantigens from all possible open reading frames of ∼120K human fusion genes in future versions

A Novel Integrated Approach to Predicting Cancer Immunotherapy Efficacy

Immunotherapies have revolutionized cancer treatment modalities; however, predicting clinical response accurately and reliably remains challenging. Neoantigen load is considered as a fundamental genetic determinant of therapeutic response. However, only a few predicted neoantigens are highly immunogenic, with little focus on intratumor heterogeneity (ITH) in the neoantigen landscape and its link with different features in the tumor microenvironment. To address this issue, we comprehensively characterized neoantigens arising from nonsynonymous mutations and gene fusions in lung cancer and melanoma. We developed a composite NEO2IS to characterize interplays between cancer and CD8+ T-cell populations. NEO2IS improved prediction accuracy of patient responses to immune-checkpoint blockades (ICBs). We found that TCR repertoire diversity was consistent with the neoantigen heterogeneity under evolutionary selections. Our defined neoantigen ITH score (NEOITHS) reflected infiltration degree of CD8+ T lymphocytes with different differentiation states and manifested the impact of negative selection pressure on CD8+ T-cell lineage heterogeneity or tumor ecosystem plasticity. We classified tumors into distinct immune subtypes and examined how neoantigen-T cells interactions affected disease progression and treatment response. Overall, our integrated framework helps profile neoantigen patterns that elicit T-cell immunoreactivity, enhance the understanding of evolving tumor-immune interplays and improve prediction of ICBs efficacy

Integrated mRNA Sequence Optimization Using Deep Learning

The coronavirus disease of 2019 pandemic has catalyzed the rapid development of mRNA vaccines, whereas, how to optimize the mRNA sequence of exogenous gene such as severe acute respiratory syndrome coronavirus 2 spike to fit human cells remains a critical challenge. A new algorithm, iDRO (integrated deep-learning-based mRNA optimization), is developed to optimize multiple components of mRNA sequences based on given amino acid sequences of target protein. Considering the biological constraints, we divided iDRO into two steps: open reading frame (ORF) optimization and 5\u27 untranslated region (UTR) and 3\u27UTR generation. In ORF optimization, BiLSTM-CRF (bidirectional long-short-term memory with conditional random field) is employed to determine the codon for each amino acid. In UTR generation, RNA-Bart (bidirectional auto-regressive transformer) is proposed to output the corresponding UTR. The results show that the optimized sequences of exogenous genes acquired the pattern of human endogenous gene sequence. In experimental validation, the mRNA sequence optimized by our method, compared with conventional method, shows higher protein expression. To the best of our knowledge, this is the first study by introducing deep-learning methods to integrated mRNA sequence optimization, and these results may contribute to the development of mRNA therapeutics

Huobahuagen tablet improves renal function in diabetic kidney disease: a real-world retrospective cohort study

ObjectiveWe aimed to explore the value of Huobahuagen tablet (HBT) in improving decreased renal function for patients with diabetic kidney disease (DKD) over time.MethodsThis was a single-center, retrospective, real-world study on eligible 122 DKD patients who continued to use HBT + Huangkui capsule (HKC) therapy or HKC therapy without interruption or alteration in Jiangsu Province Hospital of Chinese Medicine from July 2016 to March 2022. The primary observation outcomes included estimated glomerular filtration rate (eGFR) at baseline and 1-, 3-, 6-, 9-, and 12-month follow-up visits and changes in eGFR from baseline (ΔeGFR). Propensity score (PS) and inverse probability treatment weighting (IPTW) were used to control for confounders.ResultseGFR was significantly higher in the HBT + HKC group than in the HKC alone group at the 6-, 9-, and 12-month follow-up visits (p = 0.0448, 0.0002, and 0.0037, respectively), indicating the superiority of HBT + HKC over HBT alone. Furthermore, the ΔeGFR of the HBT + HKC group was significantly higher than that of the HKC alone group at the 6- and 12-month follow-up visits (p = 0.0369 and 0.0267, respectively). In the DKD G4 patients, eGFR was higher in the HBT + HKC group at the 1-, 3-, 6-, 9-, and 12-month follow-up visits compared with baseline, with statistically significant differences at the 1-, 3-, and 6- month follow-up visits (p = 0.0256, 0.0069, and 0.0252, respectively). The fluctuations in ΔeGFR ranged from 2.54 ± 4.34 to 5.01 ± 5.55 ml/min/1.73 m2. Change in the urinary albumin/creatinine ratio from baseline did not exhibit a significant difference between the two groups at any of the follow-up visits (p > 0.05 for all). Adverse event incidence was low in both groups.ConclusionThe findings of this study based on real-world clinical practice indicate that HBT + HKC therapy exhibited better efficacy in improving and protecting renal function with a favorable safety profile than HKC therapy alone. However, further large-scale prospective randomized controlled trials are warranted to confirm these results

Circulating extracellular vesicles are strongly associated with cardiovascular risk markers

Background: Extracellular vesicles (EVs) are submicron membrane-bound vesicles released from various cells, which are emerging as a potential novel biomarker in cardiovascular diseases (CVDs) due to their procoagulatory and prothrombotic properties. However, there is little information about the relationships between circulating EVs and conventional and thrombogenic risk markers of CVDs. Objective: To investigate the relationships between circulating EVs, conventional cardiovascular risk markers and thrombogenic markers in subjects with moderate risk of CVDs. Design: Subjects (n=40) aged 40-70 years with moderate risk of CVDs were recruited and assessed for body mass index, blood pressure and plasma lipid profile, as well as platelet aggregation, clot formation, thrombin generation and fibrinolysis. Numbers of circulating EVs were assessed by Nanoparticle Tracking Analysis and flow cytometry. A range of assays were used to assess the procoagulatory activity of plasma and circulating EVs. Results: Circulating EV numbers were positively associated with body mass index, blood pressure, plasma triacylglycerol concentration and overall CVD risk. Higher circulating EV numbers were also associated with increased thrombin generation and enhanced clot formation, and EVs isolated from subjects with moderate CVD risk promoted thrombin generation ex vivo. Higher numbers of endothelial-derived EVs were associated with a greater tendency for clot lysis. Plasma triacylglycerol concentration and diastolic blood pressure independently predicted circulating EV numbers, and EV numbers independently predicted aspects of thrombin generation and clot formation and 10-year CVD risk. Conclusion: Circulating EVs were strongly associated with both conventional and thrombogenic risk markers of CVDs, and also with overall CVD risk, highlighting a potentially important role for EVs in CVDs