Fragmented QRS complex could predict all-cause mortality in patients with connective tissue disease-associated pulmonary arterial hypertension.

OBJECTIVES: To investigate the prognostic impact and pathophysiological characteristics of fragmented QRS complex (fQRS) on patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). METHODS: This was a multicentre retrospective study recruiting 141 patients with CTD-PAH diagnosed by right heart catheterization (114 cases in the discovery cohort and 27 cases in the validation cohort). fQRS and ST-T change were detected on conventional 12-lead electrocardiogram (ECG). Patients were followed up every 3 months to update their status and the primary end point was all-cause death. Clinical information and ECG characteristics were compared between survival and death groups and Kaplan-Meier curve was used for survival analysis. RESULTS: There were significant differences in age, gender, 6-min walk distance, NT-proBNP, WHO class, presence of fQRS and presence of ST-T change in inferior leads between survival group and death group. Inferior fQRS and ST-T change were significantly associated with right ventricular (RV) dilatation and reduced RV ejection fraction (RVEF). Kaplan-Meier curve showed that all-cause mortality was higher in CTD-PAH with fQRS (p= 0.003) and inferior ST-T change (p= 0.012). Low- and intermediate-risk CTD-PAH with inferior ST-T change had higher all-cause mortality (p= 0.005). The prognostic value of fQRS and inferior ST-T change was validated in external validation cohort. CONCLUSION: The presence of inferior fQRS and ST-T change could predict poor prognosis in CTD-PAH. CLINICAL TRIAL REGISTRATION NUMBER: NCT05980728, https://clinicaltrials.gov.

Antioxidant, aroma, and sensory characteristics of Maillard reaction products from Urechis unicinctus hydrolysates: development of food flavorings.

To develop food flavorings with a delicious taste and an anti-oxidation effect, in this study, the glucose Maillard reaction was used for hydrolysates of Urechis unicinctus. The various biological activities of Maillard reaction products (MRPs) and their antioxidant capacity were evaluated. The results showed that the unique fishy odor substances of seafood in MRPs were reduced, indicating that the Maillard reaction improved the flavor of the hydrolysate of Urechis unicinctus. Meanwhile, MRPs exhibited more competitive radical scavenging activities compared to the hydrolysate. Moreover, MRPs demonstrated a considerable potential to protect against 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress in a cell model in vitro and in a zebrafish model in vivo. Finally, a novel food flavoring was produced with MRPs as raw material, while the sensory qualities were deemed acceptable. In consequence, during industrial production, MRPs of Urechis unicinctus hydrolysate act as a high-quality raw material for functional flavorings and provide an effective way for the utilization of marine resources.

Effect of fermentation using different lactic acid bacteria strains on the nutrient components and mineral bioavailability of soybean yogurt alternative.

Introduction: Analysis of the composition of yogurt alternatives (YAs) during fermentation provides critical information for evaluating its quality and nutritional attributes. Method: We investigated the effects of homotypic (HO) and heterotypic (HE) lactic acid bacteria on the nutritional and mineral bioavailabilities of soybean YA (SYA) during fermentation. Result: The acidic amino acid (Glu, Asp) and organic acid contents in HO-fermented YA were increased from 2.93, 1.71, and 7.43 mg/100 g to 3.23, 1.82, and 73.47 mg/100 g, respectively. Moreover, both HO and HE lactic acid bacteria fermentation enhanced mineral absorptivity. They altered the molecular speciation of minerals from a large molecular type (2,866 Da) to a small molecular type (1,500 Da), which was manifested in a time-dependent manner. Furthermore, YA substantially increased the bone mass in a zebrafish osteoporosis model, further highlighting the potential of lactic acid bacterial fermentation for mineral bioavailability. Discussion: This study provides a foundation for understanding the effects of fermentation conditions on the composition and bioavailability of minerals in YA and can assist in its production.

Calcium-binding properties, stability, and osteogenic ability of phosphorylated soy peptide-calcium chelate.

Introduction: Bioactive peptides based on foodstuffs are of particular interest as carriers for calcium delivery due to their safety and high activity. The phosphorylated peptide has been shown to enhance calcium absorption and bone formation. Method: A novel complex of peptide phosphorylation modification derived from soybean protein was introduced, and the mechanism, stability, and osteogenic differentiation bioactivity of the peptide with or without calcium were studied. Result: The calcium-binding capacity of phosphorylated soy peptide (SPP) reached 50.24 ± 0.20 mg/g. The result of computer stimulation and vibration spectrum showed that SPP could chelate with calcium by the phosphoric acid group, carboxyl oxygen of C-terminal Glu, Asp, and Arg, and phosphoric acid group of Ser on the SPP at a stoichiometric ratio of 1:1, resulting in the formation of the complex of ligand and peptide. Thermal stability showed that chelation enhanced peptide stability compared with SPP alone. Additionally, in vitro results showed that SPP-Ca could facilitate osteogenic proliferation and differentiation ability. Discussion: SPP may function as a promising alternative to current therapeutic agents for bone loss.

Preparation and Characterization of Multilayer pH-Responsive Hydrogel Loaded Ganoderma lucidum Peptides.

To develop a safe, targeted, and efficient assembly of a stable polypeptide delivery system, in this work, chitosan, sodium alginate, and sodium tripolyphosphate were used as materials for the preparation of hydrogels. M-SCT hydrogels were prepared by ionic gelation and the layer-by-layer (LBL) method. The composite hydrogels exhibited excellent pH sensitivity and Ganoderma lucidum peptides (GLP) loading capacity. The prepared hydrogels were characterized and evaluated. The internal three-dimensional network structure of the hydrogel was observed by scanning electron microscopy (SEM), and Fourier transform infrared (FT-IR) spectroscopy confirmed the electrostatic interactions among the components. X-ray diffraction (XRD) was used to observe the crystal structure of the hydrogel. The maximum peptide encapsulation efficiency was determined to be 81.73%. The digestion stability and thermal stability of M-SCT hydrogels loaded GLP were demonstrated to be improved. The amount of peptides released from the GLP/M-SCT-0.75 hydrogels in simulated gastric fluid was lower than 30%. In addition, the ABTS assays showed that the free radical scavenging ability of the GLP/M-SCT-0.75 hydrogels confirmed the efficacy of the hydrogels in retaining the antioxidant activity of GLP. The study suggested the M-SCT-0.75 hydrogels had a great deal of potential as a peptide carrier for oral delivery.

Identification of key biomarkers associated with immune cells infiltration for myocardial injury in dermatomyositis by integrated bioinformatics analysis.

BACKGROUND: Dermatomyositis (DM) is an acquired autoimmune disease that can cause damage to various organs, including the heart muscle. However, the mechanisms underlying myocardial injury in DM are not yet fully understood. METHODS: In this study, we utilized publicly available datasets from the Gene Expression Omnibus (GEO) database to identify hub-genes that are enriched in the immune system process in DM and myocarditis. Weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs) analysis, protein-protein interaction (PPI), and gene ontology (GO) analysis were employed to identify these hub-genes. We then used the CIBERSORT method to analyze immune cell infiltration in skeletal muscle specimens of DM and myocardium specimens of myocarditis respectively. Correlation analysis was performed to investigate the relationship between key genes and infiltrating immune cells. Finally, we predicted regulatory miRNAs of hub-genes through miRNet and validated their expression in online datasets and clinical samples. RESULTS: Using integrated bioinformatics analysis, we identified 10 and 5 hub-genes that were enriched in the immune system process in the database of DM and myocarditis respectively. The subsequent intersections between hub-genes were IFIT3, OAS3, ISG15, and RSAD2. We found M2 macrophages increased in DM and myocarditis compared to the healthy control, associating with the expression of IFIT3, OAS3, ISG15, and RSAD2 in DM and myocarditis positively. Gene function enrichment analysis (GSEA) showed that IFIT3, OAS3, ISG15, and RSAD2 were mainly enriched in type I interferon (IFN) signaling pathway, cellular response to type I interferon, and response to type I interferon. Finally, we verified that the expression of miR-146a-5p was significantly higher in the DM with myocardial injury than those without myocardial injury (p = 0.0009). CONCLUSION: Our findings suggest that IFIT3, OAS3, ISG15, and RSAD2 may play crucial roles in the underlying mechanism of myocardial injury in DM. Serum miR-146a-5p could be a potential biomarker for myocardial injury in DM.

Isolation, characterization, and molecular docking analyses of novel calcium-chelating peptide from soy yogurt and the study of its calcium chelation mechanism.

BACKGROUND: Calcium is an essential dietary mineral nutrient for humans. Digestive instability limits the bioavailability of calcium ions. Peptide-calcium chelate has been proven to excite higher calcium absorption than amino acid-calcium chelate, organic and inorganic calcium. Soy yogurt, which is produced via liquid-state fermentation using lactic acid bacteria, has a high amount of bioavailable calcium. In this study, a novel peptide with high calcium binding affinity was purified and identified from soy yogurt. The binding mechanism of peptide and calcium was then analyzed by bioinformatics and spectral analysis. Furthermore, the effect of the novel peptide on gastrointestinal stability by the Caco-2 cell model and calcium bioavailability in vivo were investigated by the zebrafish model. RESULTS: The results showed that a novel peptide was purified and identified as DEDEQIPSHPPR (CBP). Calcium ions probably coordinate with Glu-2 and Glu-4 carboxyl groups via salt bridges and interact with Asp-1, Asp-3, and Arg-12 in CBP via charge pairing. The calcium binding activity of the CBP was 36.64 ± 0.04 mg g-1 . Fourier transform infrared (FTIR) spectra showed that calcium spontaneously bound to the amino group nitrogen and oxygen atoms of the carboxyl group. The binding mode is either bidentate or unidentate, depending on the circumstances. More importantly, the CBP peptide substantially increased the bone mass in a zebrafish osteoporosis model. CONCLUSION: The more glutamic acid and aspartic acid, the high was the calcium affinity with peptide. Soy yogurt-derived peptides can be used as carriers of calcium ions throughout the gastrointestinal tract, which may be clinically useful for osteoporosis therapy. © 2022 Society of Chemical Industry.

The diagnostic value of serum YKL-40 for myocardial involvement in idiopathic inflammatory myopathy.

OBJECTIVE: To investigate the diagnostic value of serum chitinase-3-like-1 protein (YKL-40) levels for myocardial involvement in idiopathic inflammatory myopathies (IIM). METHODS: A total of 74 patients with definite IIM who visited Jiangsu Province People's Hospital between May 2018 and January 2022 were enrolled in this retrospective study. Baseline clinical evaluation, laboratory index, electrocardiogram (ECG), echocardiography (ECHO) and cardiac magnetic resonance (CMR) parameters were collected. Serum YKL-40 of all participants was determined by ELISA. Receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of YKL-40 in assessing myocardial involvement in IIM patients. RESULTS: 1. YKL-40 concentration was significantly higher in IIM patients with myocardial injury than without myocardial injury.2. Multivariate logistic regression analysis demonstrated that serum YKL-40 was an independent risk factor for myocardial involvement in IIM.3. YKL-40 > 66.4 ng/ml (AUC = 0.85, 95 % CI 0.75-0.95) predicted myocardial injury in IIM with a sensitivity of 0.75 and specificity of 0.95. CONCLUSION: Serum YKL-40 could serve as a potential biomarker to predict myocardial injury in IIM patients.

Physicochemical, Textural, and Sensorial Properties of Soy Yogurt as Affected by Addition of Low Acyl Gellan Gum.

Soy yogurt is plant-based dairy of great nutritional interest that is widely accepted in developing countries as a milk alternative. Poor stability has been an urgent problem to solve of soy yogurt products over past several years. The present study aimed to construct multiple network composite gel by adding low acyl gellan gum (LAG) to improve the stability. The effect of addition of LAG on property of soy yogurt was investigated by determining water holding capacity, texture, rheology, particle size, and zeta potential. The results showed that water holding capacity was significantly higher than control. The soy yogurt with 0.1% LAG had a stable gel network with much gel strength and viscosity, and strengthened interaction between complex gel. The addition of LAG increased the particle size and decreased zeta potential. Furthermore, sensory properties were acceptable. Therefore, during industrial production, LAG could act as an appropriate stabilizer to inhibit poor body and bring more desirable sensory characteristics of soy yogurt.

Novel Soy Peptide CBP: Stimulation of Osteoblast Differentiation via TßRI-p38-MAPK-Depending RUNX2 Activation.

DEDEQIPSHPPR, the calcium-binding peptide (CBP) identified in soy yogurt, was proven to be a potential cofactor in osteoporosis prevention in our previous study, but the mechanism was unknown. In this study, the activity of alkaline phosphatase (ALP) and osteocalcin (OCN), the regulation of RUNX2, and the expression of TßRI were investigated to elucidate the underlying mechanism. The results show that CBP upregulated ALP activity and OCN concentration and increased the expression of RUNX2 and the activation of the MAPK signaling pathway. Similarly, the expression of osteogenesis-related genes in osteoblasts also increased upon CBP treatment. Moreover, the CBP-induced enhancement of ALP activity and phosphorylation levels in the p38 pathway was inhibited by treatment with a p38 inhibitor (SB203538) and TßRI inhibitor (SB431542), respectively, suggesting that p38 and TßRI were involved in the osteogenic action. Based on the signaling pathways, the intracellular calcium concentration was significantly elevated by CBP, which was correlated with the increased behavioral functions and the relative fluorescence intensity of the bone mass. These findings suggest that CBP stimulates osteoblast differentiation and bone mineralization through the activation of RUNX2 via mechanisms related to the TßRI-p38-MAPK signaling pathways, further highlighting CBP's important potential for treating osteoporosis.

Calcium Binding Mechanism of Soybean Peptide with Histidine Alteration by Molecular Docking Analysis and Spectroscopic Methods.

Histidine (His) carries a unique heteroaromatic imidazole side chain and plays an irreplaceable role in peptides and proteins. With the current study, we aimed to determine the characteristics and functional activities of the bone density of soy peptide-calcium complexes in which a His residue was replaced by Leu (CBP-H). Soybean peptide (CBP-H) was chemically synthesized, the binding mechanism between CBP-H and calcium ions in combination was determined with bioinformatics and spectroscopy analysis, and the difference between CBP and CBP-H was investigated. Finally, we analyzed the effect of CBP and CBP-H on osteoblasts in vitro. The results showed that CBP-H could bind to calcium ions, and the calcium coordinated with the carboxyl groups of Asp and Glu in the peptide. The nitrogen atoms of the amino group and the oxygen atoms of the carboxyl group in CBP-H significantly contributed to the coordination with Ca2+. Furthermore, the binding capacity was 36.48 ± 0.09 mg/g, similar to CBP. However, both CBP and CBP-H could promote osteogenic activity, the activity of CBP-H was 127.147%, lower than CBP (121.777%). While it had the same ability to promote intracellular calcium concentration, CBP-H could upregulate 150.12% calcium ions into the intracellular, and the rate of the rise of CBP was 158.91%, further highlighting the potential of His residues for binding calcium and treating osteoporosis.