Understanding the Factors Influencing the Ability of Calcium-Binding Peptides to Promote Calcium Absorption

The objective of this research was to determine the factors that influence the ability of calcium-binding peptides, obtained through in silico enzymatic hydrolysis of whey proteins, to promote calcium absorption. Isothermal titration calorimetry and density functional theory calculations revealed that all of the investigated peptides could spontaneously bind calcium through an entropy-driven endothermic binding reaction via their terminal and side-chain carboxyl groups at physiological pH. Among the investigated peptides, tripeptide EAC demonstrated the strongest ability to promote calcium absorption, with a calcium ion activity-based binding constant of 209 L/mol and a promotion factor of 2.57. The ability of calcium-binding peptides to promote calcium absorption was not correlated with their calcium-binding constants but rather with their chemical hardness and ionization potential. Machine learning modeling of all 8400 dipeptides and tripeptides indicated that those with higher log P values and aliphatic N/C-termini or aromatic C-termini were more likely to effectively promote calcium absorption. These findings provide valuable insights for the design of peptides to increase calcium bioavailability

Understanding the Factors Influencing the Ability of Calcium-Binding Peptides to Promote Calcium Absorption

The objective of this research was to determine the factors that influence the ability of calcium-binding peptides, obtained through in silico enzymatic hydrolysis of whey proteins, to promote calcium absorption. Isothermal titration calorimetry and density functional theory calculations revealed that all of the investigated peptides could spontaneously bind calcium through an entropy-driven endothermic binding reaction via their terminal and side-chain carboxyl groups at physiological pH. Among the investigated peptides, tripeptide EAC demonstrated the strongest ability to promote calcium absorption, with a calcium ion activity-based binding constant of 209 L/mol and a promotion factor of 2.57. The ability of calcium-binding peptides to promote calcium absorption was not correlated with their calcium-binding constants but rather with their chemical hardness and ionization potential. Machine learning modeling of all 8400 dipeptides and tripeptides indicated that those with higher log P values and aliphatic N/C-termini or aromatic C-termini were more likely to effectively promote calcium absorption. These findings provide valuable insights for the design of peptides to increase calcium bioavailability

Molecular Mechanisms of Peptide–Calcium Complexes in Enhancing Calcium Absorption: A Transcriptome Analysis of Caco‑2 Cells Treated with Whey Protein-Derived Peptides DAF and EAC

Calcium-binding peptides have been shown to enhance calcium absorption, but the mechanism of their action is unclear. In this study, we investigated the effects of two whey protein-derived calcium-binding peptides, DAF and EAC, on calcium absorption and gene expression in Caco-2 cells. Our findings demonstrated that both peptides enhanced calcium absorption in a time-specific and peptide-specific manner and that PEPT1, the main peptide transporter in the intestine, was not involved in this process. Transcriptome analysis revealed that the calcium-binding peptides modulated the expression of genes related to various biological processes and pathways, such as cell signaling, protein transport, hormone regulation, oxidoreductase activity, and inflammatory responses, some of which were related to the TRPV6 pathway. Furthermore, DAF and EAC appeared to influence distinct cellular processes, with DAF potentially impacting gene expression and chromatin structure, while EAC may play a role in cell division and differentiation. Both peptides were found to activate the MAPK signaling pathway, which is closely linked to calcium ion absorption. These findings elucidate the molecular mechanisms, underlying the promotion of calcium absorption by peptide–calcium complexes, and suggest the potential applications of calcium-binding peptides as functional food ingredients with enhanced bioavailability and efficacy

Understanding the Factors Influencing the Ability of Calcium-Binding Peptides to Promote Calcium Absorption

The objective of this research was to determine the factors that influence the ability of calcium-binding peptides, obtained through in silico enzymatic hydrolysis of whey proteins, to promote calcium absorption. Isothermal titration calorimetry and density functional theory calculations revealed that all of the investigated peptides could spontaneously bind calcium through an entropy-driven endothermic binding reaction via their terminal and side-chain carboxyl groups at physiological pH. Among the investigated peptides, tripeptide EAC demonstrated the strongest ability to promote calcium absorption, with a calcium ion activity-based binding constant of 209 L/mol and a promotion factor of 2.57. The ability of calcium-binding peptides to promote calcium absorption was not correlated with their calcium-binding constants but rather with their chemical hardness and ionization potential. Machine learning modeling of all 8400 dipeptides and tripeptides indicated that those with higher log P values and aliphatic N/C-termini or aromatic C-termini were more likely to effectively promote calcium absorption. These findings provide valuable insights for the design of peptides to increase calcium bioavailability

Dynamic manipulation of graphene plasmonic skyrmions

With the characteristics of ultrasmall, ultrafast and topological protection, optical skyrmions has great prospects in application of high intensity data stroage, high resolution microscopic imaging and polarization sensing. The flexible control of the optical skyrmions is the premise of practical application. At present, the manipulation of optical skyrmions usually relies upon the change of spatial structure, which results in a limited-tuning range and a discontinuous control in the parameter space. Here, we propose continuous manipulation of the graphene plasmons skyrmions based on the electrotunable properties of graphene. By changing the Fermi energy of one pair of the standing waves and the phase of the incident light can achieve the transformation of the topological state of the graphene plasmons skyrmions, which can be illustrated by the change of the skyrmion number from 1 to 0.5. The direc manipulation of the graphene plasmons skyrmions is demonstrated by the simulation results based on the finite element method. Our work suggests a feasible way to flexibly control the optical skyrmions topological field, which can be used for novel integrated photonics devices in the future

Table1_Investigation of the biomarkers involved in ectopic ossification: The shared mechanism in ossification of the spinal ligament.XLSX

Background: Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are multifactor diseases characterized by progressively ectopic ossification in the spinal ligament. However, the shared ossification mechanism of OPLL and OLF remains to be elucidated. The study aims to investigate the common biomarkers related to ectopic ossification and the potential molecular regulatory mechanism.Methods: Microarray and RNA-seq datasets were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) from OPLL and OLF were identified to construct the protein-protein interaction (PPI) network. Furthermore, the hub intersection genes were screened and the diagnostic performance was assessed in the external OLF and OPLL cohorts. We also depicted the landscape of immune cell infiltration and m6A modification meanwhile further estimating the relationship with BMP4.Results: A total of nine up-regulated DEGs and 11 down-regulated DEGs were identified to construct the PPI networks. The integrative bioinformatic analysis defined five hub genes (BMP4, ADAMTS4, HBEGF, IL11, and HAS2) as the common risk biomarkers. Among them, BMP4 was the core target. ROC analysis demonstrated a high diagnostic value of the hub genes. Moreover, activated B cells were recognized as shared differential immune infiltrating cells and significantly associated with BMP4 in OPLL and OLF. Meanwhile, a strong correlation was detected between the expression pattern of the m6A regulator METTL3 and BMP4.Conclusion: This study first identified BMP4 as the shared core biomarker in the development of OPLL and OLF. Activated B cells and m6A writer METTL3 might be involved in the osteogenesis process mediated by BMP4. Our findings provide insights into the pathogenesis in the ossification of the spinal ligament and unveil the potential therapeutic targets.</p

Table1_Association between CILP and IL-1α polymorphisms and phenotype-dependent intervertebral disc degeneration susceptibility: A meta-analysis.DOCX

Background: The relationship between CILP (1184T>C) and IL-1α(+889C/T) polymorphisms and intervertebral disc degeneration (IDD) have been explored in several studies but the results were conflicting. The aim of the study was to evaluate and synthesize the currently available data on the association between CILP (1184T>C) and IL-1α(+889C/T) polymorphisms and susceptibility of phenotype-dependent radiologic IDD (RIDD) and symptomatic intervertebral disk herniation (SIDH).Methods: A computerized literature search was in PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure database, and Web of Science. The pooled results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Moreover, the false-positive report probability (FPRP) test and trial sequential analysis (TSA) were applied to estimate the significant results.Results: Our evidence demonstrated that IL-1α(+889C/T) was significant associated with RIDD (allele model: OR = 1.34, 95%CI 1.03–1.74, p = 0.029) and SIDH (allele model: OR = 1.28, 95% CI 1.03–1.60, p = 0.028). However, the results were not noteworthy under the FPRP test and TSA analysis. Additionally, CILP (1184T>C) polymorphism was significantly associated with RIDD with adequate evidence (allele model: OR = 1.27, 95% CI 1.09–1.48, p = 0.002) instead of SIDH.Conclusion: The current meta-analysis illustrated firm evidence that CILP (1184T>C) polymorphism was significantly associated with the susceptibility of RIDD. However, the significant associations between IL-1α(+889C/T) and RIDD and SIDH were less credible. Thus, more multi-center studies with diverse populations were required to verify the results.</p

Table3_Investigation of the biomarkers involved in ectopic ossification: The shared mechanism in ossification of the spinal ligament.XLS

Background: Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are multifactor diseases characterized by progressively ectopic ossification in the spinal ligament. However, the shared ossification mechanism of OPLL and OLF remains to be elucidated. The study aims to investigate the common biomarkers related to ectopic ossification and the potential molecular regulatory mechanism.Methods: Microarray and RNA-seq datasets were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) from OPLL and OLF were identified to construct the protein-protein interaction (PPI) network. Furthermore, the hub intersection genes were screened and the diagnostic performance was assessed in the external OLF and OPLL cohorts. We also depicted the landscape of immune cell infiltration and m6A modification meanwhile further estimating the relationship with BMP4.Results: A total of nine up-regulated DEGs and 11 down-regulated DEGs were identified to construct the PPI networks. The integrative bioinformatic analysis defined five hub genes (BMP4, ADAMTS4, HBEGF, IL11, and HAS2) as the common risk biomarkers. Among them, BMP4 was the core target. ROC analysis demonstrated a high diagnostic value of the hub genes. Moreover, activated B cells were recognized as shared differential immune infiltrating cells and significantly associated with BMP4 in OPLL and OLF. Meanwhile, a strong correlation was detected between the expression pattern of the m6A regulator METTL3 and BMP4.Conclusion: This study first identified BMP4 as the shared core biomarker in the development of OPLL and OLF. Activated B cells and m6A writer METTL3 might be involved in the osteogenesis process mediated by BMP4. Our findings provide insights into the pathogenesis in the ossification of the spinal ligament and unveil the potential therapeutic targets.</p

Table2_Investigation of the biomarkers involved in ectopic ossification: The shared mechanism in ossification of the spinal ligament.XLS

Background: Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are multifactor diseases characterized by progressively ectopic ossification in the spinal ligament. However, the shared ossification mechanism of OPLL and OLF remains to be elucidated. The study aims to investigate the common biomarkers related to ectopic ossification and the potential molecular regulatory mechanism.Methods: Microarray and RNA-seq datasets were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) from OPLL and OLF were identified to construct the protein-protein interaction (PPI) network. Furthermore, the hub intersection genes were screened and the diagnostic performance was assessed in the external OLF and OPLL cohorts. We also depicted the landscape of immune cell infiltration and m6A modification meanwhile further estimating the relationship with BMP4.Results: A total of nine up-regulated DEGs and 11 down-regulated DEGs were identified to construct the PPI networks. The integrative bioinformatic analysis defined five hub genes (BMP4, ADAMTS4, HBEGF, IL11, and HAS2) as the common risk biomarkers. Among them, BMP4 was the core target. ROC analysis demonstrated a high diagnostic value of the hub genes. Moreover, activated B cells were recognized as shared differential immune infiltrating cells and significantly associated with BMP4 in OPLL and OLF. Meanwhile, a strong correlation was detected between the expression pattern of the m6A regulator METTL3 and BMP4.Conclusion: This study first identified BMP4 as the shared core biomarker in the development of OPLL and OLF. Activated B cells and m6A writer METTL3 might be involved in the osteogenesis process mediated by BMP4. Our findings provide insights into the pathogenesis in the ossification of the spinal ligament and unveil the potential therapeutic targets.</p

Additional file 5 of Uncovering the gene regulatory network of type 2 diabetes through multi-omic data integration

Additional file 5: Table S1: MSEA top pathways. Table S2: Scores of pathways after applying 12 topological algorithms. Table S3: Detailed information of key drivers in wKDA network. Table S4: The details of hub genes. Table S5: The details of TFs. Table S6: Detailed results of drug repositioning results