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Background: Heart failure is primarily characterized by damage to the structure and function of the heart. Ferroptosis represents a form of programmed cell death, and studies indicate that it constitutes one of the primary mechanisms underlying cardiomyocyte death in heart failure. Calycosin, a natural compound derived from astragalus, exhibits various pharmacological properties, including anti-ferroptosis, antioxidant effects, and cardiovascular protection. Nonetheless, the specific role of Calycosin in the treatment of ferroptosis in heart failure remains poorly understood., Objective: This study aims to elucidate the regulatory effect of Calycosin on ferroptosis and its influence on the treatment mechanisms of heart failure through in vivo and in vitro experiments., Methods: A rat model of heart failure was induced using doxorubicin, and the cardiac function was evaluated through cardiac ultrasound examination and NT-Pro BNP detection. Myocardial injury was assessed using H&E staining and Masson staining. The extent of mitochondrial damage was evaluated through transmission electron microscopy. Concurrently, the level of ferroptosis was analyzed by measuring ferroptosis markers, including MDA, ferrous ions, the GSH/GSSG ratio, and GPX4 activity. Subsequently, the molecular mechanism by which Calycosin exerts its therapeutic effects in heart failure was investigated through immunofluorescence and Western blotting. Finally, H9c2 cardiomyocytes were treated with doxorubicin to simulate myocardial injury, and the mechanism by which Calycosin mediates its effects in the treatment of heart failure was further verified through Nrf2 gene silencing., Results: Calycosin significantly improves cardiac function in rats, reduces serum NT-Pro BNP levels, and alleviates myocardial cell damage. Additionally, it significantly decreases the levels of ferroptosis in myocardial tissue, as confirmed through transmission electron microscopy and the assessment of ferroptosis markers, including MDA, ferrous ions, GSH, and GPX4 activity. At the molecular level, Calycosin exerts its effects by activating the Nrf2/SLC7A11/GPX4 signaling pathway, evidenced by the upregulation of Nrf2, SLC7A11, GPX4, GSS, and GCL protein expression. This process substantially enhances the antioxidant capacity of rat myocardial tissue and effectively suppresses ferroptosis in myocardial cells. The results obtained from both in vivo and in vitro experiments are consistent. Notably, when Nrf2 is silenced, the protective effect of Calycosin on the myocardium is markedly diminished., Conclusion: Calycosin effectively treats doxorubicin-induced cardiac injury, and its therapeutic effect is likely closely associated with the activation of the Nrf2/SLC7A11/GPX4 signaling pathway and the inhibition of ferroptosis in myocardial cells. Consequently, Calycosin, as a promising compound against doxorubicin-induced cardiotoxicity, warrants further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Shi, Yu, Yuan, Guo, Liu, Xue and Li.)

Alcoholic liver disease (ALD) is a serious health threat. Soybean meal peptide (SMP) supplementation may protect against this damage; however, the potential mechanism underlying the specific sequence of SMPs is unclear. Protein-protein interaction and proteomic analyses are effective methods for studying functional ingredients in diseases. This study aimed to investigate the potential mechanism of action of the peptide Gly-Thr-Tyr-Trp (GTYW) on ALD using protein-protein interaction and proteomic analyses. These results demonstrate that GTYW influenced the targets of glutathione metabolism (glutathione-disulfide reductase, glutathione S-transferase pi 1, and glutathione S-transferase mu 2). It also regulated the expression of targets related to energy metabolism and amino acid conversion (trypsin-2, cysteine dioxygenase type-1, and F6SJM7). Amino acid and lipid metabolisms were identified based on Gene Ontology annotation. These results indicate that GTYW might affect alcohol-related liver disease signaling pathways. This study provides evidence of the protective and nutritional benefits of SMPs in ALD treatment., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier Ltd.)

Aging is a major risk factor for cardiovascular diseases (CVD), and mitochondrial autophagy impairment is considered a significant physiological change associated with aging. Endothelial cells play a crucial role in maintaining vascular homeostasis and function, participating in various physiological processes such as regulating vascular tone, coagulation, angiogenesis, and inflammatory responses. As aging progresses, mitochondrial autophagy impairment in endothelial cells worsens, leading to the development of numerous cardiovascular diseases. Therefore, regulating mitochondrial autophagy in endothelial cells is vital for preventing and treating age-related cardiovascular diseases. However, there is currently a lack of systematic reviews in this area. To address this gap, we have written this review to provide new research and therapeutic strategies for managing aging and age-related cardiovascular diseases.

Hearing loss is the third most prevalent physical condition affecting communication, well-being, and healthcare costs. Sensorineural hearing loss often occurs first in the high-frequency region (basal turn), then towards the low-frequency region (apical turn). However, the mechanism is still unclear. Supporting cells play a critical role in the maintenance of normal cochlear function. The function and supporting capacity of these cells may be different from different frequency regions. Hensen's cells are one of the unique supporting cell types characterized by lipid droplets (LDs) in the cytoplasm. Here, we investigated the morphological and gene expression differences of Hensen's cells along the cochlear axis. We observed a gradient change in the morphological characteristics of Hensen's cells along the cochlear tonotopic axis, with larger and more abundant LDs observed in apical Hensen's cells. Smart-seq2 RNA-seq revealed differentially expressed genes (DEGs) between apical and basal Hensen's cells that clustered in several pathways, including unsaturated fatty acid biosynthesis, cholesterol metabolism, and fatty acid catabolism, which are associated with different energy storage capacities and metabolic potential. These findings suggest potential differences in lipid metabolism and oxidative energy supply between apical and basal Hensen's cells, which is consistent with the morphological differences of Hensen's cells. We also found differential expression patterns of candidate genes associated with hereditary hearing loss (HHL), noise-induced hearing loss (NIHL), and age-related hearing loss (ARHL). These findings indicate functional heterogeneity of SCs along the cochlear axis, contribute to our understanding of cochlear physiology and provide molecular basis evidence for future studies of hearing loss.

Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function and potentially triggering apoptosis or necrosis. This process is closely correlated with the onset of many diseases. Evidence suggests that the phenolic hydroxyl groups in food-borne plant polyphenols (FPPs) make them effective antioxidants capable of preventing diseases triggered by cell membrane LP. Proper dietary intake of FPPs can attenuate cellular oxidative stress, especially damage to cell membrane phospholipids, by activating the Nrf2/GPx4 pathway. Nuclear factor E2-related factor 2 (Nrf2) is an oxidative stress antagonist. The signaling pathway regulated by Nrf2 is a defense transduction pathway of the organism against external stimuli such as reactive oxygen species and exogenous chemicals. Glutathione peroxidase 4 (GPx4), under the regulation of Nrf2, is the only enzyme that reduces cell membrane lipid peroxides with specificity, thus playing a pivotal role in regulating cellular ferroptosis and counteracting oxidative stress. This study explored the Nrf2/GPx4 pathway mechanism, antioxidant activity of FPPs, and mechanism of LP. It also highlighted the bioprotective properties of FPPs against LP and its associated mechanisms, including (i) activation of the Nrf2/GPx4 pathway, with GPx4 potentially serving as a central target protein, (ii) regulation of antioxidant enzyme activities, leading to a reduction in the production of ROS and other peroxides, and (iii) antioxidant effects on LP and downstream phospholipid structure. In conclusion, FPPs play a crucial role as natural antioxidants in preventing LP. However, further in-depth analysis of FPPs coregulation of multiple signaling pathways is required, and the combined effects of these mechanisms need further evaluation in experimental models. Human trials could provide valuable insights into new directions for research and application.

Gene therapy for monogenic auditory neuropathy (AN) has successfully improved hearing function in target gene-deficient mice. Accurate genetic diagnosis can not only clarify the etiology but also accurately locate the lesion site, providing a basis for gene therapy and guiding patient intervention and management strategies. In this study, we collected data from a family with a pair of sisters with prelingual deafness. According to their auditory tests, subject Ⅱ-1 was diagnosed with profound sensorineural hearing loss (SNHL), Ⅱ-2 was diagnosed with AN, Ⅰ-1 was diagnosed with high-frequency SNHL, and Ⅰ-2 had normal hearing. Using whole-exome sequencing (WES), one nonsense mutation, c.4030C>T (p.R1344X), and one missense mutation, c.5000C>A (p.A1667D), in the OTOF (NM_001287489.1) gene were identified in the two siblings. Their parents were heterozygous carriers of c.5000C>A (father) and c.4030C>T (mother). We hypothesized that c.5000C>A is a novel pathogenic mutation. Thus, subject Ⅱ-1 should also be diagnosed with AN caused by OTOF mutations. These findings not only expand the OTOF gene mutation spectrum for AN but also indicate that WES is an effective approach for accurately diagnosing AN., Competing Interests: The authors have no conflicts of interest to disclose., (2024, International Research and Cooperation Association for Bio & Socio - Sciences Advancement.)

Despite its effectiveness in treating diabetic cardiomyopathy (DCM), Qigui Qiangxin Mixture (QGQXM) remains unclear in terms of its active ingredients and specific mechanism of action. The purpose of this study was to explore the active ingredients and mechanism of action of QGQXM in the treatment of DCM through the comprehensive strategy of serum pharmacology, network pharmacology and combined with experimental validation. The active ingredients of QGQXM were analyzed using Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q/TOF-MS). Network pharmacology was utilized to elucidate the mechanism of action of QGQXM for the treatment of DCM. Finally, in vivo validation was performed by intraperitoneal injection of STZ combined with high-fat feeding-induced DCM rat model. A total of 25 active compounds were identified in the drug-containing serum of rats, corresponding to 121 DCM-associated targets. GAPDH, TNF, AKT1, PPARG, EGFR, CASP3, and HIF1 were considered as the core therapeutic targets. Enrichment analysis showed that QGQXM mainly treats DCM by regulating PI3K-AKT, MAPK, mTOR, Insulin, Insulin resistance, and Apoptosis signaling pathways. Animal experiments showed that QGQXM improved cardiac function, attenuated the degree of cardiomyocyte injury and fibrosis, and inhibited apoptosis in DCM rats. Meanwhile, QGQXM also activated the PI3K/AKT signaling pathway, up-regulated Bcl-2, and down-regulated Caspase9, which may be an intrinsic mechanism for its anti-apoptotic effect. This study preliminarily elucidated the mechanism of QGQXM in the treatment of DCM and provided candidate compounds for the development of new drugs for DCM., (© 2024. The Author(s).)

Background: In the face of continued growth in the elderly population, the need to understand and combat age-related cardiac decline becomes even more urgent, requiring us to uncover new pathological and cardioprotective pathways., Methods: We obtained the aging-related genes of heart failure through WGCNA and CellAge database. We elucidated the biological functions and signaling pathways involved in heart failure and aging through GO and KEGG enrichment analysis. We used three machine learning algorithms: LASSO, RF and SVM-RFE to further screen the aging-related genes of heart failure, and fitted and verified them through a variety of machine learning algorithms. We searched for drugs to treat age-related heart failure through the DSigDB database. Finally, We use CIBERSORT to complete immune infiltration analysis of aging samples., Results: We obtained 57 up-regulated and 195 down-regulated aging-related genes in heart failure through WGCNA and CellAge databases. GO and KEGG enrichment analysis showed that aging-related genes are mainly involved in mechanisms such as Cellular senescence and Cell cycle. We further screened aging-related genes through machine learning and obtained 14 key genes. We verified the results on the test set and 2 external validation sets using 15 machine learning algorithm models and 207 combinations, and the highest accuracy was 0.911. Through screening of the DSigDB database, we believe that rimonabant and lovastatin have the potential to delay aging and protect the heart. The results of immune infiltration analysis showed that there were significant differences between Macrophages M2 and T cells CD8 in aging myocardium., Conclusion: We identified aging signature genes and potential therapeutic drugs for heart failure through bioinformatics and multiple machine learning algorithms, providing new ideas for studying the mechanism and treatment of age-related cardiac decline., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Wang, Hou, Xue, Liu and Li.)

Bioactive peptides have been shown to affect cell membrane fluidity, which is an important indicator of the cell membrane structure and function. However, the underlying mechanism of egg white-derived bioactive peptide regulation of cell membrane fluidity has not been elucidated yet. The cell membrane fluidity was investigated by giant unilamellar vesicles in the present study. The results showed that peptides TCNW, ADWAK, ESIINF, VPIEGII, LVEEY, and WKLC connect to membranes through intermolecular interactions, such as hydrogen bonding and regulated membrane fluidity, in a concentration-dependent way. In addition, peptides prefer to localize in the hydrophobic core of the bilayers. This study provides a theoretical basis for analyzing the localization of egg white bioactive peptides in specific cell membrane regions and their influence on the cell membrane fluidity.

Background: Ischemic heart failure (IHF) is a serious complication after acute myocardial infarction (AMI). Understanding the mechanism of IHF after AMI will help us conduct early diagnosis and treatment., Methods: We obtained the AMI dataset GSE66360 and the IHF dataset GSE57338 from the GEO database, and screened overlapping genes common to both diseases through WGCNA analysis. Subsequently, we performed GO and KEGG enrichment analysis on overlapping genes to elucidate the common mechanism of AMI and IHF. Machine learning algorithms are also used to identify key biomarkers. Finally, we performed immune cell infiltration analysis on the dataset to further evaluate immune cell changes in AMI and IHF., Results: We obtained 74 overlapping genes of AMI and IHF through WGCNA analysis, and the enrichment analysis results mainly focused on immune and inflammation-related mechanisms. Through the three machine learning algorithms of LASSO, RF and SVM-RFE, we finally obtained the four Hub genes of IL1B, TIMP2, IFIT3, and P2RY2, and verified them in the IHF dataset GSE116250, and the diagnostic model AUC = 0.907. The results of immune infiltration analysis showed that 8 types of immune cells were significantly different in AMI samples, and 6 types of immune cells were significantly different in IHF samples., Conclusion: We explored the mechanism of IHF after AMI by WGCNA, enrichment analysis, and immune infiltration analysis. Four potential diagnostic candidate genes and therapeutic targets were identified by machine learning algorithms. This provides a new idea for the pathogenesis, diagnosis, and treatment of IHF after AMI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Universal newborn hearing screening (UNHS) and audiological diagnosis are crucial for children with congenital hearing loss (HL). The objective of this study was to analyze hearing screening techniques, audiological outcomes and risk factors among children referred from a UNHS program in Beijing. A retrospective analysis was performed in children who were referred to our hospital after failing UNHS during a 9-year period. A series of audiological diagnostic tests were administered to each case, to confirm and determine the type and degree of HL. Risk factors for HL were collected. Of 1839 cases, 53.0% were referred after only transient evoked otoacoustic emission (TEOAE) testing, 46.1% were screened by a combination of TEOAE and automatic auditory brainstem response (AABR) testing, and 1.0% were referred after only AABR testing. HL was confirmed in 55.7% of cases. Ears with screening results that led to referral experienced a more severe degree of HL than those with results that passed. Risk factors for HL were identified in 113 (6.1%) cases. The main risk factors included craniofacial anomalies (2.7%), length of stay in the neonatal intensive care unit longer than 5 days (2.4%) and birth weight less than 1500 g (0.8%). The statistical data showed that age (P < 0.001) and risk factors, including craniofacial anomalies (P < 0.001) and low birth weight (P = 0.048), were associated with the presence of HL. This study suggested that hearing screening plays an important role in the early detection of HL and that children with risk factors should be closely monitored., (© 2023. The Author(s).)

Background: The presence of residual cardiovascular risk is an important cause of cardiovascular events. Despite the significant advances in our understanding of residual cardiovascular risk, a comprehensive analysis through bibliometrics has not been performed to date. Our objective is to conduct bibliometric studies to analyze and visualize the current research hotspots and trends related to residual cardiovascular risk. This will aid in understanding the future directions of both basic and clinical research in this area., Methods: The literature was obtained from the Web of Science Core Collection database. The literature search date was September 28, 2022. Bibliometric indicators were analyzed using CiteSpace, VOSviewer, Bibliometrix (an R package), and Microsoft Excel., Result: A total of 1167 papers were included, and the number of publications is increasing rapidly in recent years. The United States and Harvard Medical School are the leading country and institution, respectively, in the study of residual cardiovascular risk. Ridker PM and Boden WE are outstanding investigators in this field. According to our research results, the New England Journal of Medicine is the most influential journal in the field of residual cardiovascular risk, whereas Atherosclerosis boasts the highest number of publications on this topic. Analysis of keywords and landmark literature identified current research hotspots including complications of residual cardiovascular risk, risk factors, and pharmacological prevention strategies., Conclusion: In recent times, global attention toward residual cardiovascular risk has significantly increased. Current research is focused on comprehensive lipid-lowering, residual inflammation risk, and dual-pathway inhibition strategies. Future efforts should emphasize strengthening international communication and cooperation to promote the comprehensive evaluation and management of residual cardiovascular risk., (© 2023. The Author(s).)

The role of immune cells in the pathogenesis of ischemic heart failure (IHF) is well-established. However, identifying key genes in patients with IHF remains a challenge. We obtained two IHF datasets from the GEO database (GSE76701 and GSE21610), and identified four potential diagnostic candidate genes for IHF by using bioinformatics and machine learning algorithms, namely RNASE2, MFAP4, CHRDL1, and KCNN3. We constructed nomogram and validated the diagnostic value of these genes on additional GEO datasets (GSE57338). The results showed that these four genes had high diagnostic value (area under the curve value of 0.961). Furthermore, our immune infiltration analysis revealed the presence of three dysregulated immune cells in IHF, namely macrophages M2, monocytes, and T cells gamma delta. We also explored the potential molecular mechanisms of IHF. These findings provide new insights into the pathogenesis, diagnosis, and treatment of IHF., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Natural multicomponent peptides with abundant bioactivity, varied sizes, and tunable interaction potential are available for rational designing novel self-assembled delivery carriers. Herein, we exploited zein-hyaluronic acid nanoparticles (Z-HA NPs) with a predetermined ordered structure as precursor templates to induce the self-assembly of egg white-derived peptides (EWDP) to generate stable spherical architectures for the enhancement of curcumin (Cur). The resulting Z-EWDP-HA NPs encapsulated hydrophobic Cur through robust hydrogen bonding and hydrophobic interactions with high encapsulation efficiency (97.38% at pH 7.0). The NPs presented superior Cur aqueous solubility, redispersibility, and photothermal stability. More importantly, the self-assembled EWDP could exert synergistic antioxidant activity with Cur and enhance the bioaccessibility of Cur. Meanwhile, the favorable biocompatibility and membrane affinity of EWDP further prolonged residence and time-controlled release feature of Cur in the small intestine. Precursor template-induced multicomponent peptides' self-assembly provides an efficient and controllable strategy for co-enhanced bioactivity and self-assembly capacity of peptides, which could dramatically broaden the functionalization of multicomponent peptides hydrolyzed from natural food proteins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Changes in storage temperature and time alter the functional properties of egg white powder (EWP) and determine its quality and shelf-life, finally affecting the consumer acceptance of the products made from EWP. In the present study, the EWP samples were stored at four different temperatures (-20, 4, 25 and 37 °C) for 60 days, and then the protein structural, physical and functional properties of EWP were measured and assessed further for correlation with storage conditions using heatmap., Results: The viscosity of the EWP solution increased after 30 days. Foaming ability and rheological properties increased first and then decreased compared to untreated samples with the prolonged storage time. Correlation analysis results indicated that the gel hardness, water holding capacity, foaming ability, emulsifying ability, particle size, dispersibility and viscosity of EWP were significantly related to storage time (P < 0.05). Only the gelation properties of EWP stored at 37 °C for 60 days changed significantly and were negatively related to its moisture content (P < 0.05). Additionally, the random coil content of EWP was positively correlated with particle size, moisture content, solubility and gel properties, whereas β-sheet was negatively correlated with them., Conclusion: Compared to other temperatures, the functional properties of EWP were relatively stable under 4 °C. Therefore, the low temperature (4 °C) was selected as the most suitable storage temperature for EWP. The results of the present study could provide a theoretical basis for the shelf-life extension of EWP. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Concurrent screening has been proven to provide a comprehensive approach for management of congenital deafness and prevention of ototoxicity. The SLC26A4 gene is associated with late-onset hearing loss and is of great clinical concern. For much earlier detection of newborns with deafness-causing mutations in the SLC26A4 gene, the Beijing Municipal Government launched a chip for optimized genetic screening of 15 variants of 4 genes causing deafness based on a chip to screen for 9 variants of 4 genes, and 6 variants of the SLC26A4 gene have now been added. To ascertain the advantage of a screening chip including 15 variants of 4 genes, the trends in concurrent hearing and genetic screening were analyzed in 2019 and 2020. Subjects were 76,460 newborns who underwent concurrent hearing and genetic screening at 24 maternal and child care centers in Beijing from January 2019 to December 2020. Hearing screening was conducted using transiently evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAE), or the automated auditory brainstem response (AABR). Dried blood spots were collected for genetic testing and 15 variants of 4 genes, namely GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened for using a DNA microarray platform. The initial referral rate for hearing screening decreased from 3.60% (1,502/41,690) in 2019 to 3.23% (1,124/34,770) in 2020, and the total referral rate for hearing screening dropped form 0.57% (236/41,690) in 2019 to 0.54% (187/34,770) in 2020, indicating the reduced false positive rate of newborn hearing screening and policies to prevent hearing loss conducted by the Beijing Municipal Government have had a significant effect. Positivity according to genetic screening was similar in 2019 (4.970%, 2,072/41,690) and 2020 (4.863%,1,691/34,770), and the most frequent mutant alleles were c.235 del C in the GJB2 gene, followed by c.919-2 A > G in the SLC26A4 gene, and c.299 del AT in the GJB2 gene. In this cohort study, 71.43% (5/7) of newborns with 2 variants of the SLC26A4 gene were screened for newly added mutations, and 28.57% (2/7) of newborns with 2 variants of the SLC26A4 gene passed hearing screening, suggesting that a screening chip including 15 variants of 4 genes was superior at early detection of hearing loss, and especially in early identification of newborns with deafness-causing mutations in the SLC26A4 gene. These findings have clinical significance.

Background: Free fatty acids (FFAs) could induce inflammatory responses via various pathways. Ferroptosis is characterized by the accumulation of lipid peroxidation products and fatal reactive oxygen species derived from iron accumulation, which may be an upstream event in the inflammatory injuries., Objectives: To investigate the involvement of ferroptosis during the FFAs-induced pathological hair cell inflammatory injuries and its underlying mechanisms., Material and Methods: We utilized House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line as an in vitro model. The palmitate acid (PA) was utilized as a substitute for FFA, with cotreatment with ferroptosis inducer RSL3 and ferroptosis inhibitor Fer-1. Cell viability, lactase dehydrogenase (LDH) release, the expressions of ferroptosis-related factors such as glutathione peroxidase-4 (GPX4), solute carrier family 7 member 11 (SLC7A11), as well as toll-like receptor 4 (TLR4), ferric ion and reactive oxygen species (ROS), and partial inflammatory cytokines were measured., Results: PA treatment might induce ferroptosis in HEI-OC1 cells, manifested as decreased cell viability, upregulated LDH release, iron overload, and ROS accumulation. Several inflammatory cytokines including IL-1β, IL-6, IL-1β, IL-6, TNF-α, MCP-1, IL-13, IL-12 p40, CCL5, G-CSF, and GM-CSF were upregulated compared to the Ctr group, while GPX4 and SLC7A11 were downregulated. The expression of TLR4 in the inflammatory pathway was also upregulated. Besides, these changes were further exacerbated by RSL3 cotreatment and abolished by Fer-1 cotreatment., Conclusions and Significance: Ferroptosis inhibition could alleviate the PA-induced inflammatory injuries via inactivation of TLR4 signaling pathway in HEI-OC1 cell line.

Objective: To investigate the clinical audiological characteristics of children referred from maternal and child institutions and analyze the high risk factors of hearing loss, so as to provide scientific basis for further improvement of children's ear and hearing care. Methods: The subjects of this study were 868 children who were referred by maternal and child institutions in Beijing to the otology outpatient of Beijing Tongren Hospital, Capital Medical University for hearing diagnosis. All subjects underwent acoustic immittance, auditory brainstem response, distortion products otoacoustic emission and other audiological tests. Children were divided into groups according to the age of diagnosis: 0-<3 months group（242 cases）, 3-<6 months group（328 cases）, 6-<12 months group（180 cases）, ≥12 months group（118 cases）, the results of hearing diagnosis, hearing loss degree and types, the relationship between high risk factors and hearing loss in each group were compared and analyzed. Results: The age of diagnosis of 868 children was（7.13±8.29） months. 488 cases with hearing loss accounted for 56.22% and 380 cases with normal hearing accounted for 43.78%. Proportion of different degree of hearing loss of 792 ears from high to low was as follows: mild, 366 ears（46.21%）; moderate, 214 ears（27.02%）; severe, 151 ears（19.07%）; profound, 61 ears（7.70%）. There were statistically significant differences in the proportion of different hearing loss degree among 0-<3 months group, 3-<6 months group, 6-<12 months group and ≥12 months group（ P <0.001）. Pairwise comparison between groups showed that the proportion of mild hearing loss of 0-<3 months group was higher than that in the other three groups（ P <0.05）, there was no significant difference of moderate hearing loss among all groups（ P >0.05）, the proportion of severe hearing loss of ≥12 months group was higher than that of 0-<3 months group（ P <0.05）. The proportion of profound hearing loss with 0-<3 months group was lower than the other three groups（ P <0.05）. In 792 ears with hearing loss, sensorineural hearing loss accounted for 67.42%, conductive hearing loss accounted for 20.71% and mixed hearing loss accounted for 11.87%. Among 98 cases with high risk factors for hearing loss, 58 cases（59.18%） were diagnosed with hearing loss. The incidence of hearing loss with high risk factors ranked from high to low was: craniofacial malformation（93.75%）, family history/congenital genetic syndrome（61.11%）, neonatal intensive care unit（NICU） hospitalization（46.43%） and others（20.00%）. Conclusion: Referrals from maternal and child institutions play an important role in the early detection of children with mild to moderate sensorineural hearing loss. Children with craniofacial malformation, family history/congenital genetic syndrome, hospitalization history of NICU and other high risk factors have a high incidence of hearing loss and should be attached with great importance., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Fermented egg-milk peptides (FEMPs) could alleviate the symptoms of inflammatory diseases but the underlying regulating mechanism of effective ingredients is unclear now. Our research was designed to confirm the protective function of FEMP, then analyze the potential targets and pathways that could be regulated by digested FEMP (dFEMP). The results showed that FEMP could ease the inflammatory symptoms in the colon, repair the damage of inflammation, and decrease the level of pro-inflammatory cytokines (decreased by 31.81% TNF-α, 60.20% IL-1β, 85.65% IL-6). The results of in silico experiments revealed that dFEMP could influence many inflammation-related targets. Most targets affected the inflammation-related function and participated in the inflammatory signaling pathways, such as the T cell receptor (TCR) signaling pathway. Besides, molecular docking results revealed that hydrogen-bonding and salt bridges played vital roles in the dFEMP-target interactions. Combining in vivo experiments with in silico experiments, this study can prove a new theory for research between the bioactive peptides and inflammation.

The Maillard reaction reduces the gastrointestinal digestibility of ovalbumin (OVA) in vitro. However, the regulatory effects of OVA and its Maillard reaction products (MRPs) on gut microbiota disorders remain unknown. In this study, the influence of OVA and its MRPs on the modulation of gut microbiota in mice with dextran sulfate sodium (DSS)-induced colitis was investigated. The results revealed that OVA and its MRPs intake could alleviate the symptoms of colitis and improve the richness and diversity of the gut microbiota. Moreover, the results revealed that the Maillard reaction would block the release of lysine and essential amino acids in vivo, but they variously regulated the gut microbiota and the levels of short-chain fatty acids (SCFAs) due to their indigestible properties. These findings provide a basic theory for the rational utilization of OVA and its MRPs as nutraceutical food ingredients in regulating the gut microbiota for maintaining intestinal health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2022. Published by Elsevier B.V.)

Membrane phase separation forms liquid-ordered (Lo) and liquid-disordered (Ld) phases and is involved in cellular processes and functions. Our previous study has confirmed that peptides can regulate phase separation by increasing the Lo phase. However, the specific mechanisms underlying the phase separation regulation of peptides remain poorly understood. This study aimed to explore the effect of soybean meal peptides on phase separation and illustrate the correlation between phase regulation and membrane localization of the peptides. Phase separation was studied by giant unilamellar vesicles (GUVs), and membrane localization of the peptides was detected by steady-state fluorescence quenching. Our results revealed that peptides YYK, CLA, and SLW enhanced the Lo phase while WLQ decreased the Lo phase. The localization in the membrane amphiphilic region of the peptides played a crucial role in their regulation of phase separation. The more localization of the peptides (YYK, CLA, and SLW) in the membrane amphiphilic region, the stronger the capacity to increase the Lo phase., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, a nanocomposite was developed by introducing egg white-derived peptides (EWDP) into protein-polysaccharide complexes to trigger the self-assembly of EWDP for encapsulating curcumin (Cur) via the pH-driven method. In this system, EWDP could cooperate with protein-polysaccharide complexes to exert superior colloidal properties with excellent Cur aqueous solubility, redispersibility, and physical stability and act as a bioactivity amplifier to endow the delivery system with the synergistic antioxidant activity. This phenomenon was ascribed to the additional hydrophobic cavities, hydrogen bonding, and electrostatic interactions organized by EWDP. Additionally, the presence of EWDP could considerably boost the cellular antioxidant activity of Cur by decreasing reactive oxygen species (ROS) levels, improving free radical scavenging capacity, and recovering the activity of endogenous antioxidant enzymes. These findings might open up an avenue to reinforce lipophilic nutraceuticals' physicochemical properties and functionalities based on the co-assembly of food-derived peptides and protein-polysaccharide complexes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Food-derived tripeptides can relieve colitis symptoms; however, their alleviation mode has not been systematically evaluated as an alternative nutritional compound. This study aimed to reveal the potential mechanism of 8000 food-derived tripeptides against acute colitis using a computer-aided screening strategy. Forty-one potential hub targets related to colitis with a Fit score > 4.0 were screened to construct the protein-protein and protein-tripeptide network based on the PharmMapper database and STRING software (Ver. 11.5). In addition, 30 significant KEGG signaling pathways with p-values < 0.001 that the 41 hub targets mainly participated in were identified using DAVID software (Ver. 6.8), including inflammatory, immunomodulatory, and cell proliferation and differentiation-related signaling pathways, particularly in the Ras- and PI3K-Akt signaling pathways. Furthermore, molecular docking was performed using the Autodock against majorly targeted proteins (AKT1, EGFR, and MMP9) with the selected 52 tripeptides. The interaction model between tripeptides and targets was mainly hydrogen-bonding and hydrophobic interactions, and most of the binding energy of the tripeptide target was less than −7.13 kcal/mol. This work can provide valuable insight for exploring food-derived tripeptide mechanisms and therapeutic indications.

In this work, by using high throughput virtual screening and bioactivity assays, this work revealed that three natural compounds, mulberrin (Mul) exhibiting the highest anti-CYP51 activity, isoxanthohumol and (s)-isopsoralen markedly inhibited 14α-demethylase (a pivotal biosynthetic enzyme involved in the biosynthesis of ergosterol) in Colletotrichum gloeosporioides. Results of computational biology analysis demonstrated that, among the three inhibitors bound to the catalytic pocket of CYP51, Mul showed a closer distance with heme in CYP51 and a stronger binding free energy with CYP51. In vitro tests, Mul demonstrated excellent anti-Colletotrichum gloeosporioides activity by inhibiting CYP51 activity. Notably, Mul treatment decreased the bioactivity of CYP51, thereby increasing cell membrane permeability and cell death. Moreover, Mul treatment significantly prolonged the preservation period of fruits. These results suggest that Mul suppresses anthracnose in postharvest mango by inhibiting the growth of Colletotrichum gloeosporioides and can be used as a potential natural preserving agent., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: School-aged children may experience hearing loss and emotional problems. Previous studies have shown a bidirectional relationship between hearing loss and emotional problems in the elderly population, and we aimed to analyze the association between hearing thresholds and emotional problems in school-aged children., Methods: Based on the Beijing Child Growth and Health Cohort (PROC) study, the hearing screenings were conducted in November 2019 using pure tone audiometry. A total of 1,877 parents completed the Strengths and Difficulties Questionnaire (SDQ) to assess children's emotional and behavioral status. We used generalized linear regression analysis to assess the potential association of emotional problems with hearing thresholds, based on multiple imputed datasets with a sample size of 1,914., Results: The overall pass rate of hearing screening was 91.5%. The abnormal rate of SDQ total difficulties was 55.8%. Emotional symptoms were positively associated with left ear average hearing thresholds (β = 0.24, 95% CI : 0.08-0.40), and right ear average hearing thresholds (β = 0.18, 95% CI : 0.04-0.32). Conduct problems, hyperactivity/inattention, peer problems, and prosocial behaviors had no association with the pass rate of the hearing screening. Regarding emotional symptoms, boys with many fears and who are easily scared coincided with increased right ear average hearing thresholds (β = 0.67, 95% CI : 0.01-1.33). Girls having many worries, frequently feeling unhappy and downhearted were positively associated with left and right ear average hearing thresholds, respectively (β = 0.96, 95% CI : 0.20-1.73; β = 0.72, 95% CI : 0.07-1.37)., Conclusions: The co-occurrence of hearing problems and emotional problems of children aged 6-8 in Beijing attracts attention. It is important to address undiscovered hearing loss and emotional problems from the perspective of comorbidity driving factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiao, Amaerjiang, Wang, Li, Zunong, En, Zhao, Wen, Yu, Huang and Hu.)

Background: This study aimed to assess the quality of global guidelines or consensus statements for newborn and childhood hearing screening, as well as to compare various guidelines between other countries and China., Methods: A PROSPERO registered systematic review (number CRD42021242198) was conducted. Multiple electronic databases and government websites including PubMed, EMBASE, Web of Science, CENTRAL, Cochrane Library, and BMJ Best Practice were searched from inception until May 2021. The latest national and international guidelines, consensus statements, technical specifications, and recommendations regarding newborn or childhood hearing screening that were published in Chinese or English medical journals or elsewhere with the full version available online. The following information was extracted independently by two reviewers for comparative analysis: titles, authors, publication year, country, the source organization, and main key recommendations using systems for assigning the level of evidence and strength of recommendations. The quality of the guidelines was assessed by three independent reviewers using the Appraisal of Guidelines for Research and Evaluation, 2nd edition. Intraclass correlation coefficients (ICCs) were calculated to assess among-reviewer agreement., Results: We assessed 15 newborn and 6 childhood hearing screening guidelines, respectively. Most newborn guidelines recommend the 1-3-6 guidelines and pre-discharge screening; however, the specific screening times differ. 93.33% of newborn hearing guidelines recommend "primary screening-re-screening-diagnosis-intervention" for well-babies while 73.33% of the guidelines recommend "initial screening-diagnosis-intervention" for newborns in neonatal intensive care unit (NICU); 33.33% of the newborn hearing guidelines recommended initial screening coverage of > 95% while 46.66% did not mention it. Further, 26.66% of the newborn hearing guidelines recommended a referral rate to diagnosis within 4% while 60% did not mention it. Regarding childhood hearing screening guidelines, the screening populations differed across guidelines (age range: 0-9 years); most guidelines recommend pediatric hearing screening for all preschoolers. Only 50% of the guidelines specify screening and re-screening techniques, including pure-tone hearing screening, OAE, tympanometry, and others. The "Clarity of Presentation" domain achieved the highest mean score, and the lowest was "Editorial Independence" both in newborn and childhood guidelines. Overall score of newborn hearing screening guidelines ranged from 3 (2018 Europe) to 7 (2019 America), with an average score of 5.33. Average score of childhood hearing screening guidelines was 4.78, with the score ranging from 4 (2017 England, 2012 Europe, 2016 WHO) to 6.67 (2011 America). ICC analysis revealed excellent agreement across 21 guidelines (> 0.75)., Conclusions: These findings indicated newborn hearing screening guidelines had superior quality over childhood ones. Comparative analysis suggested that recommendations of the Chinese newborn and pediatric hearing screening protocols are consistent with the mainstream international opinion. Moreover, this analysis demonstrated that "Editorial Independence" and "Stakeholder Involvement" have the greatest opportunities for improvement. These results may help to advance the quality of hearing screening guidelines in clinical practice and guide evidence-based updates., (© 2022. The Author(s).)

The food-derived peptides hydrolyzed from native food protein matrix exhibited various bioactivities and multimeric structures, which make them the promising well-defined nanoplatforms candidates to co-deliver themselves with other bioactive compounds. In this study, zein-egg white derived peptides-chitosan (Z-EWDP-CS) ternary nanoparticles (NPs) were successfully fabricated by the spontaneous assembly to enhance the stability and bioactivity of curcumin (Cur). The novel ternary NPs exhibited a typical nano-spherical structure (138.63 nm, 40.50 mV), and adorable encapsulation efficiency (EE, 93.87%) for Cur. FTIR, XRD and DSC results verified that Cur changed from a crystalline state to an amorphous state, and was successfully entrapped in the cavity of Z-EWDP-CS NPs. Furthermore, the thermal stability, photochemical stability, salt stability, and antioxidant activity were considerably improved in the NPs after the addition of EWDP. Our results demonstrate that the food-derived peptides could be an ideal affinity agent for the co-delivery of themselves with hydrophobic nutraceuticals., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Egg white peptides (EWPs) can be effectively used to alleviate and treat inflammatory diseases due to their anti-oxidation, anti-inflammation, and microbiota regulation capabilities. A dextran sodium sulfate (DSS)-induced colitis model was used to clarify the regulatory effects of EWPs on colitis. Forty-three peptide sequences were identified from EWPs using LC-MS/MS. The results demonstrated that EWPs decreased the levels of pro-inflammatory cytokines and the extent of crypt damage in a dose-dependent manner. 16S rRNA gene sequencing results indicated that 200 mg/kg EWPs significantly increased the relative abundance of beneficial bacteria Lactobacillus and Candidatus&#95;Saccharimonas, and reduced the relative abundance of pathogenic bacteria Ruminiclostridium and Akkermansia. In addition, the degree of correlation between pro-inflammatory cytokines and microbiota was as follows: interleukin (IL)-1β > IL-8 > IL-6 > tumor necrosis factor-α To summarize, EWPs contributed to the alleviation of colitis symptoms and the intestinal injury through anti-inflammatory effects, repair of intestinal mucosa, and modulation of gut microbiota., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study aimed was to explore the hepatoprotective potential of soybean meal peptides (SPs) against alcohol-induced liver injury and investigate the underlying mechanisms through transcriptome analysis. The chemical antioxidant analysis of SPs exhibited potent ABTS radical scavenging capacity (11.94 ± 0.41 mg TE/100 mg peptide), ferric reducing antioxidant power (6.42 ± 0.32 mmol Fe 2+ /100 mg peptide), and oxygen radical absorption capacity (14.78 ± 0.01 mg TE/100 mg peptide). Moreover, SPs increased cell viability and reduced intracellular reactive oxygen species levels in Caco-2 cells by H 2 O 2 -induced, and without cytotoxicity. In the mice model, preintervention with SPs reduced the levels of aspartate transaminase/alanine transaminase, total cholesterol, triglyceride and malondialdehyde by alcohol-induced, meanwhile, increased the levels of total superoxide dismutase, glutathione and catalase by alcohol-induced. Histological analysis showed that SPs alleviated the liver injury by alcohol-induced and no toxic effects on the kidneys. According to transcriptome analysis, 1737 genes were significantly differentially expressed (1076 up-regulated and 661 down-regulated) after SPs pretreatment. The main functions of these genes were related to inflammation, lipid metabolism and oxidation. The findings from the present study suggested that SPs produced positive hepatoprotection and showed potential to be used as a dietary supplement or an ingredient of functional food., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The mechanism between food gelation and its digestibility has attracted increasing attention over the past few decades. This study aimed to evaluate the effect of glycation degree on the gelation and digestibility of egg white gel (EWG) using an in vitro model and a multi-scale characterization of gel structure. Results showed that EWG glycated with increasing d-ribose by covalent bonds exhibited better gelling properties and lower in vitro digestibility according to the appearance of soluble proteins and peptides. Besides, glycation preference for ovotransferrin at lysine might be important for regulating gel structure and proteolysis accessibility via the ratio of fibrous and granular aggregates. Moreover, gel structure was predominant over amino acids modification for digestibility. Binding disorder and steric hindrance could ascribe to the lower digestibility of gels. These findings are enlightening for the formulation and production of food matrix with controlled digestibility through glycation in food and related pharmaceutical fields., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To analyze the current status of newborn deafness gene screening from 2016 to 2017 in multiple regions of China, and to provide a reference for further promotion and application. Method: The "newborn deafness gene screening questionnaire" was sent to 41 institutions in eastern, central and western China after expert demonstration. The survey content included status of genetic screening, screening methods, the number of screenings, and the status of positive detections from January 1st, 2016 to December 31th, 2017. Each institution returned the questionnaire, the investigator conducted data verification and quality sampling. Finally, we performed analysis of screening methods and the positive detection rate of each gene on questionnaires with complete data. Result: Forty-one questionnaires were sent out and 41 were returned, the questionnaire return rate was 100%, in which 12 questionnaires were complete. Of the 41 institutions, 15 carried newborn deafness gene screening, with a rate of 36.59%（15/41）. The highest rate was in the east（72.22%, 13/18）, and the differences among the regions were statistically significant. As for the screening methods, among 12 questionnaires with complete data, 9 variants in 4 genes and 20 variants in 4 genes accounted for the highest proportion, both with the rate of 33.33%（4/12）, followed by 15 variants in 4 genes（25%, 3/12） and 5 variants in 3 genes（8.34%, 1/12）. A total of 340, 521 neonates were included in the study, and 17, 036 were positive for screening, with a positive rate of 5.00%. Among them, the single heterozygous mutation rate of GJB2 gene was 2.43%（8269/340, 521）, the biallele mutation rate was 0.02%（56/340, 521）,the single heterozygous mutation rate of SLC26A4 gene was 1.99%（6771/340, 521）, the biallele mutation rate was 0.01%（39/340, 521）,the single heterozygous mutation rate of GJB3 gene was 0.33%（1140/340, 521）, the mitochondrial 12SrRNA gene mutation rate was 0.22%（746/340, 521） and the double-gene heterozygous mutation rate was 0.004%（15/340, 521）. Conclusion: From 2016 to 2017, the newborn deafness gene screening is more extensive in the eastern region of China than in the central and western regions. In institutions that have carried out deafness gene screening, 9 variants in 4 genes and 20 variants in 4 genes are widely used; the GJB2 gene and SLC26A4 gene mutations are the most common. The results could provide references for areas where deafness gene screening is about to be performed., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Oxidative stress is frequently associated with hypertension. However, the studies on antihypertensive peptides usually focus on ACE inhibitory activity and ignore antioxidant activity of bioactive peptides. In our research, we optimized enzymatic hydrolysis condition of egg white protein. After that we evaluated both the antioxidant and the ACE-inhibitory activity in vitro of egg white hydrolysates and its purified fractions. Four peptides, LAPYK, SVIRW, PKSVIRW, and ADWAK, which can match to ovotransferrin were identified from fraction with the highest bioactivity. Among them, LAPYK possessed the strongest activity with ABTS scavenging IC 50 of 5.29 ± 0.24 µM, ORAC of 1.50 ± 0.04 µM TE/µM, ACE-inhibitory IC 50 of 12.65 ± 1.34 µM. For further, we explored inhibitory mechanism of LAPYK against ACE. Research on bifunctional peptides is helpful for the application of antihypertensive peptides. PRACTICAL APPLICATIONS: At present, the therapeutic drugs for hypertension usually focus on a single target, but the pathogenesis of hypertension is multifactorial, and the combined treatment of multiple targets may have a better therapeutic effect. Compared with commercially available drugs, food-derived bioactive peptides have lower side effects, as well as exhibit multi-bioactivities more easily. Exploration of bifunctional peptides with both ACE inhibitory and antioxidant activity provides new ideas for the treatment of hypertension., (© 2020 Wiley Periodicals LLC.)

New Delhi metallo-β-lactamase (NDM-1) is the most recent addition to the class of metallo-β-lactamases (MBLs). This enzyme leads to antibiotic resistance in clinical treatments owing to its exertion of hydrolysis activity in almost all clinically available β-lactam antibiotics. Consequently, inhibitors targeting NDM-1 have attracted considerable research attention. However, progress has been slow regarding the study of the quantitative structure-activity relationship (QSAR) of NDM-1 inhibitors. In this study, a three-dimensional QSAR (3 D-QSAR) for NDM-1 inhibitors was established using Topomer CoMFA. The multiple correlation coefficients of the fitting model, leave-one-out cross validation, and external validation were found to be 0.761, 0.976, and 0.972, respectively. Topomer Search was used to design 16 new molecules that inhibit NDM-1 using R-group search from ZINC databases, 10 of which had comparatively high activities against NDM-1. The results indicate that Topomer CoMFA and Topomer Search can be used to design new NDM-1 inhibitors and guide the design of new NDM-1 drugs with good predictive capability. Furthermore, from molecular modeling and binding free-energy calculation, it was found that the newly designed molecules can bind to the catalytic region of NDM-1. Additionally, the newly designed inhibitors formed strong interactions with Ile35, Met67, Phe70, Trp93, His122, His189, Cys208, and His250 around the Zn 2+ -centered active region of NDM-1. These findings will facilitate the development of more effective NDM-1 inhibitors for use as potential antibacterial agents.Communicated by Ramaswamy H. Sarma.

The data article refers to the paper "A study on the preparation of chitosan-tripolyphosphate nanoparticles and its entrapment mechanism for egg white derived peptides" [1]. Data presented here include impact factors (chitosan molecular weights, pH values, chitosan-tripolyphosphate mass ratio, and chitosan concentration) on the preparation and colloidal properties of chitosan-tripolyphosphate nanoparticles. Data also refer to the effect of impact factors (chitosan molecular weight, chitosan concentration, peptides-chitosan mass ratio and pH values) on the entrapment efficiency and entrapment capacity of chitosan-tripolyphosphate nanoparticles loading with egg white derived peptides. Data also involve the size and zeta potential change after the egg white derived peptides entrapped in chitosan-tripolyphosphate nanoparticles. Additionally, data exhibit the free amino group and surface hydrophobicity of egg white derived peptides with different molecular weights., (© 2019 Published by Elsevier Inc.)

EMS Agenda 2050 follows the original EMS Agenda for the Future and EMS Education Agenda for the Future. These visionary documents discussed and described learning content, requirements, and design of EMS education. This article written by members of the EMS Agenda 2050 Technical Expert Panel highlights the content in the preceding agendas for the future and content from EMS Agenda 2050 in an effort to provide a summarized guide for new and existing EMS education curriculums.

The entrapment of peptides can effectively improve their bioavailability and commercial application. This research sought to investigate the mechanism of entrapment of egg white derived peptides (EWDP) loaded in chitosan-tripolyphosphate (CS-TPP) nanoparticles (NPs). It was shown that CS molecular weight (MW), pH, CS-TPP mass ratio and CS concentration can all affect the size, polydispersity index and zeta potential of CS-TPP NPs. Moreover, these factors, as well as different MW and CS mass ratio of peptides also had an influence on entrapment efficiency (EE). Furthermore, peptides influenced the zeta potential after they were loaded in the CS-TPP NPs. This suggested that the peptide charged groups were in different locations relative to the CS-TPP NPs surfaces. FTIR analysis indicated that the peptides interacted with CS-TPP NPs through strong hydrogen bonds and electrostatic interactions. These findings are important for designing delivery systems used for commercial production of entrapped peptides with enhanced attributes., (Copyright © 2019. Published by Elsevier Ltd.)

The treatment of bacterial infections is currently threatened by the emergence of pathogenic bacteria producing β-lactamase, which catalyzes the hydrolysis of β-lactams. Although the hydrolysis of the substrate nitrocefin by a metallo-β-lactamase, namely β-lactamase N1 from USA300 (a typical methicillin-resistant Staphylococcus aureus), has previously been reported in the literature, its mechanism remains elusive. Here, we show that molecular modeling and quantum-mechanical/molecular mechanics (QM/MM) calculations describing the complex of β-lactamase N1 with nitrocefin (the substrate of β-lactamase N1) can predict the catalytic mechanism of nitrocefin hydrolysis by β-lactamase N1. Molecular dynamics simulation shows that the catalytic reaction begins with hydrogen bond formation between Gln171 and a water molecule, which is thereby captured for nitrocefin hydrolysis by β-lactamase N1. In addition, the carboxyl group coordinates Zn2 in a chelating fashion. The binding energy decompositions suggest that Phe169 anchors nitrocefin by π-stacking interactions between the benzene rings. Specifically, Phe169 and Zn2 position the nitrocefin in specific orientations. The active site of β-lactamase N1 contains two residues (Gln171 and Phe169) that we expected to be crucial for guiding the nitrocefin hydrolysis reaction. Compelling evidence is provided that the mutants F169A and Q171A show lower enzymatic activity than the wild-type protein. On the basis of the QM/MM calculations, we propose that nitrocefin hydrolysis is initiated by the interaction between the oxygen atom of water and the C18 atom of nitrocefin, leading to the opening of the four-membered ring of nitrocefin and the formation of a substrate intermediate. In the next step, a hydrogen atom transfers from the nitrogen atom to the C11 atom of nitrocefin, resulting in the stable product.

Previous studies found that the activity of Sortase A, a bacterial surface protein from Staphylococcus aureus, was inhibited by curcumin and its analogues. To explore this inhibitory mechanism, Sortase A and its inhibitors in complex systems were studied by molecular docking, molecular modelling, binding energy decomposition calculation and steered molecular dynamics simulations. Energy decomposition analysis indicated that PRO-163, LEU-169, GLN-172, ILE-182 and ILE-199 are key residues in Sortase A-inhibitor complexes. Furthermore, interactions between the methoxyl group on the benzene ring in the conjugated molecule (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and VAL-168, LEU-169 and GLN-172 induce the inhibitory activity based on the energy decomposition and distance analyses between the whole residues and inhibitors. However, because of its coiled structure, the non-conjugated molecule, tetrahydrocurcumin, with key residues in the binding sites of Sortase A, interacted weakly with SrtA, leading to the loss of inhibitory activity. Based on these results, the methoxyl group on the benzene ring in the conjugated molecule largely influenced the inhibitory activity of the Sortase A inhibitors.

Three novel egg white-derived peptides were demonstrated to display in vitro activities against the angiotensin converting enzyme (ACE). A further study was conducted to assess their anxiolytic-like effects upon spontaneously hypertensive rats (SHRs) after an oral administration of the peptides, which showed the same behavioral performance as that using an elevated plus maze (EPM). In the EPM experiment, the behavioral effects of peptides TNGIIR, RVPSL, and QIGLF were investigated at doses ranging from 5 to 50 mg kg(-1), with records of the number of entries by the rats into the open arms, the time the rats spent in the open arms, and the total amount of entries into the open + closed arms. The results showed that the peptides TNGIIR and RVPSL, in a range of 5-50 mg kg(-1), exerted an anxiolytic effect on the SHRs. These results suggested that the egg white derived peptides TNGIIR and RVPSL could be considered as possible functional food or food ingredients due to their in vivo anti-stress and anti-anxiety effects on the SHRs.

Development of angiotensin I-converting enzyme (ACE, EC 3.4.15.1) inhibitory peptides from food protein is under extensive research as alternative for the prevention of hypertension. However, it is difficult to identify peptides released from food sources. To accelerate the progress of peptide identification, a three layer back propagation neural network model was established to predict the ACE-inhibitory activity of pentapeptides derived from bovine hemoglobin by simulated enzyme digestion. The pentapeptide WTQRF has the best predicted value with experimental IC50 23.93 μM. The potential molecular mechanism of the WTQRF / ACE interaction was investigated by flexible docking.

Objectives: We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general population after adjusting for traditional cardiovascular risk factors., Methods: A population-based longitudinal cohort study from 1994 to 2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the UK. Patients aged 18-89 years of age with PsA, RA or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents and the composite outcome (MACE). Cox proportional hazards models were used to calculate the HRs for each outcome adjusted for traditional risk factors. A priori, we hypothesised an interaction between disease status and disease-modifying antirheumatic drug (DMARD) use., Results: Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=81 573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in patients with PsA not prescribed a DMARD (HR 1.24, 95% CI 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95% CI 1.28 to 1.50, DMARD: HR 1.58, 95% CI 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95% CI 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95% CI 1.17 to 1.73)., Conclusions: Cardiovascular risk should be addressed with all patients affected by psoriasis, PsA or RA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The purpose of this study was to investigate the appropriate proportion of Caco-2 and HT29 co-culture in vitro cell models for permeability studies. The results showed that the transepithelial electrical resistance values of 9:1 and 1:0 groups (263 ± 3.61 and 300 ± 7.55) after 21-day culture were >250 Ω cm(2), which were suitable for further experiments. The confocal laser microscopy showed that the group of 9:1 (Caco-2:HT29) had the highest integrity, whereas the group of 0:1 (Caco-2:HT29) exhibited the lowest. The staining study confirmed that mucus was successfully produced by HT29 cells, and it was also produced in co-cultures with Caco-2 cells model, but the Caco-2 monocultures did not have any blue staining, which made us affirm that mucus is only produced in the presence of HT29 cells. The real-time PCR results showed that the total highest expression level of ALPi and MUC5AC was the ratio of 9:1 (Caco-2:HT29) and lowest is 1:1 (Caco-2:HT29). So we concluded that 9:1 (Caco-2:HT29) is the optimal Caco-2 to HT29 ratio in the in vitro model co-culture for permeability studies.

Spray drying is a useful method for developing egg process and utilization. The objective of this study was to evaluate effects on spray drying condition of egg white. The optimized conditions were spraying flow 22 mL/min, feeding temperature 39.8 °C and inlet-air temperature 178.2 °C. Results of sulfydryl (SH) groups measurement indicated conformation structure have changed resulting in protein molecule occur S-S crosslinking phenomenon when heating. It led to free SH content decreased during spray drying process. There was almost no change of differential scanning calorimetry between fresh egg white and spray-drying egg white powder (EWP). For a given protein, the apparent SH reactivity is in turn influenced by the physico-chemical characteristics of the reactant. The phenomenon illustrated the thermal denaturation of these proteins was unrelated to their free SH contents. Color measurement was used to study browning level. EWP in optimized conditions revealed insignificant brown stain. Swelling capacity and scanning electron micrograph both proved well quality characteristic of spray-drying EWP. Results suggested spray drying under the optimized conditions present suitable and alternative method for egg processing industrial implementation. Egg food industrialization needs new drying method to extend shelf-life. The purpose of the study was to provide optimal process of healthy and nutritional instant spray-drying EWP and study quality characteristic of spray-drying EWP.

Optimized conditions were obtained by one-factor-at-a-time test (OFAT) and ternary quadratic regression orthogonal composite design (TQROCD) respectively. By pulse electric fields (PEF) technology, the process of eggshell calcium citrate malate (ESCCM), eggshell calcium citrate (ESCC) and eggshells calcium malate (ESCM) were comprehensive compared. The levels of tartrate-resistant acid phosphatase (TRAP) and the bioavailability on mice fed with eggshell calcium citrate malate (ESCCM) treated by pulsed electric field (PEF) were evaluated. Results showed that the rates of calcium dissolution of the different acids studied can be arranged as ESCCM (7.90 mg/mL)>ESCC (7.12 mg/mL)>ESCM (7.08 mg/mL) from highest to lowest rate of dissolution. At the same dose 133.0 mg kg(-1) d(-1), the levels of TRAP in the ESCCM treatment groups were significantly lower than those in ESCM and ESCC (P<0.05). Bone calcium content in the mice fed with ESCCM was generally higher than fed with ESCM and ESCC., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: Psoriasis is a Th-1/17 mediated inflammatory disease associated with increased risk of cardiovascular disease (CVD). Inflammation may modulate lipoprotein particle number and directly impair HDL functions, in particular reverse cholesterol transport (RCT). We sought to study how chronic in vivo inflammation modulates lipoprotein particle composition using nuclear magnetic resonance spectroscopy (NMR) and HDL efflux in psoriasis., Methods and Results: We prospectively enrolled a consecutive sample of patients with psoriasis (n = 122) and compared lipoprotein and metabolic risk factors to patients without psoriasis (n = 134). Fasting lipids, insulin, glucose were measured by standard assays, and lipoprotein concentration and size were measured by NMR. In a random subset (n = 100 each group), HDL efflux capacity was quantified using a validated ex vivo system involving the incubation of macrophages with apolipoprotein B-depleted serum from patients. Traditional lipid concentrations were similar in both groups except for HDL concentration which was lower in psoriasis (43 mg/dl (36-58) vs 50 (42-62), p < 0.01). However, NMR showed an atherogenic profile in psoriasis similar to that observed in diabetes, with significant increase in LDL particle concentration [1210.5 (1002-1498) vs 1115 (935-1291), p = 0.02] with decrease in LDL size [20.6 (20.3-21.1) vs 21.3 (20.6-21.1), p < 0.001] beyond CV risk factors and HOMA-IR (p = 0.001). Finally, HDL efflux capacity was lower in psoriasis compared to controls in fully adjusted models (beta -0.14, p = 0.001)., Conclusions: These data support a more atherogenic lipoprotein profile by NMR and decreased HDL efflux capacity in psoriasis patients compared to controls beyond CVD risk factors. The abnormal lipoprotein particle composition and HDL efflux capacity in psoriasis may provide a link between psoriasis and CVD., (Published by Elsevier Ireland Ltd.)

Psoriasis is a model Th1-mediated inflammatory disease associated with increased incidence of stroke and cardiovascular disease (CVD). The mechanism behind these associations is unknown, however abnormal HDL particle composition measured by nuclear magnetic resonance (NMR) spectroscopy has been shown to be associated with CVD. Using [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT), a validated surrogate marker of CVD, we assessed whether HDL particle size and concentration were associated with vascular inflammation in patients with psoriasis. Patients with psoriasis were prospectively enrolled (439 aortic samples from 10 patients). Lipoprotein profiles using NMR spectroscopy were obtained and the relationship between vascular inflammation within the thoracic aorta by FDG-PET/CT was analyzed for association with lipoprotein particle characteristics. The plasma total cholesterol (206 mg/dL (IQR 154-229)), LDL (105 (90-161)), and triglyceride levels were within normal range (151 (94-191)) while HDL levels were low (28.9 (27.2-31.3)); however, the NMR profile demonstrated an atherogenic profile with increased small LDL and HDL particles. Total HDL particle concentration (p<0.001) and HDL particle size (p<0.001) were associated with decreased aortic inflammation, while concentration of small HDL particles was associated with increased inflammation (p<0.001). The association of total HDL particle concentration (β -0.0113, p=0.002) and small HDL particle concentration (β 0.026, p<0.001) with aortic inflammation persisted following adjustment for CVD risk factors. Total HDL particle concentration and small HDL particle concentration were associated with vascular inflammation within the thoracic aorta in psoriasis. These findings suggest that HDL particle characteristics may play an important role in psoriatic vascular inflammation and CVD.

A bioactive peptide Arg-Val-Pro-Ser-Leu (RVPSL) obtained from egg white protein was characterized by LC-MS and further chemically synthesized by the Fmoc solid phase method and investigated in terms of its angiotensin converting enzyme (ACE)-inhibitory activity, antioxidant property, and anticoagulation activity, as well as its stability in a simulated gastrointestinal digestion. The peptide exhibited an ACE-inhibitory activity with an IC(50) value of 20 μM. Also, the peptide could efficiently quench the (1,1)-diphenyl-2-picrylhydrazyl free radicals and exhibit high anticoagulation activity with a complete inhibition at 100 mM. Moreover, the peptide has a good stability against protease digestion. These results suggest that the peptide RVPSL may have potential to be used in nutraceuticals and functional food. Practical Application:  The present research revealed a novel multifunctional peptide hydrolyzed from egg white protein. The peptide RVPSL was not only able to block the amplification of the coagulation cascade, but also able to inhibit ACE activity., (© 2011 Institute of Food Technologists®)

Background: Corn silk is a traditional Chinese herbal medicine, which has been widely used for treatment of some diseases. In this study the effects of pulsed electric field on the extraction of polysaccharides from corn silk were investigated., Results: Polysaccharides in corn silk were extracted by pulsed electric field and optimized by response surface methodology (RSM), based on a Box-Behnken design (BBD). Three independent variables, including electric field intensity (kV cm(-1) ), ratio of liquid to raw material and pulse duration (µs), were investigated. The experimental data were fitted to a second-order polynomial equation and also profiled into the corresponding 3-D contour plots. Optimal extraction conditions were as follows: electric field intensity 30 kV cm(-1) , ratio of liquid to raw material 50, and pulse duration 6 µs. Under these condition, the experimental yield of extracted polysaccharides was 7.31% ± 0.15%, matching well with the predicted value., Conclusion: The results showed that a pulsed electric field could be applied to extract value-added products from foods and/or agricultural matrix., (Copyright © 2011 Society of Chemical Industry.)

Objective: To evaluate the feasibility of using [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) to detect and quantify systemic inflammation in patients with psoriasis., Design: Case series with a nested case-control study., Setting: Referral dermatology and preventive cardiology practices., Participants: Six patients with psoriasis affecting more than 10% of their body surface area and 4 controls age and sex matched to 4 of the patients with psoriasis for a nested case-control study., Main Outcome Measures: The FDG uptake in the liver, musculoskeletal structures, and aorta measured by mean standardized uptake value, a measure of FDG tracer uptake by macrophages and other inflammatory cells., Results: FDG-PET/CT identified numerous foci of inflammation in 6 patients with psoriasis within the skin, liver, joints, tendons, and aorta. Inflammation in the joints was observed in a patient with psoriatic arthritis as well as in 1 patient with no history of joint disease or joint symptoms. In a nested case-control study, FDG-PET/CT imaging demonstrated increased vascular inflammation in multiple segments of the aorta compared with controls. These findings persisted after adjustment for traditional cardiovascular risk factors in multivariate analysis (mean β = 0.33; P < .001). Patients with psoriasis further demonstrated increased hepatic inflammation after adjusting for cardiovascular risk factors (β = 0.18; P < .001), but the association was no longer significant when adjusted for alcohol intake (β = -0.25; P = .07)., Conclusion: FDG-PET/CT is a sensitive tool for identifying inflammation and can be used to identify clinically observed inflammation in the skin and subclinical inflammation in the blood vessels, joints, and liver of patients with psoriasis.