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Angiotensin and kinin metabolic pathways are reported to be altered by many diseases, including COVID-19. Monitoring levels of these peptide metabolites is important for understanding mechanisms of disease processes. In this paper, we report dimethyl labeling of amines in peptides by addition of formal-dehyde to samples and deutero-formaldehyde to internal standards to generate nearly identical isotopic standards with 4 m/z units larger per amine group than the corresponding analyte. We apply this approach to rapid, multiplexed, absolute LC-MS/MS quantitation of renin angiotensin system (RAS) and kallikrein-kinin system (KKS) peptides in human blood serum. Limits of detection (LODs) were obtained in the low pg mL−1 range with 3 orders of magnitude dynamic ranges, appropriate for determinations of normal and elevated levels of the target peptides in blood serum and plasma. Accuracy is within ±15% at concentrations above the limit of quantitation, as validated by spike-recovery in serum samples. Applicability was demonstrated by measuring RAS and KKS peptides in serum from COVID-19 patients, but is extendable to any class of peptides or other small molecules bearing reactive –NH2 groups. [ABSTRACT FROM AUTHOR]

Next-generation single-molecule protein sequencing technologies have the potential to significantly accelerate biomedical research. These technologies offer sensitivity and scalability for proteomic analysis. One auspicious method is fluorosequencing, which involves: cutting naturalized proteins into peptides, attaching fluorophores to specific amino acids, and observing variations in light intensity as one amino acid is removed at a time. The original peptide is classified from the sequence of light-intensity reads, and proteins can subsequently be recognized with this information. The amino acid step removal is achieved by attaching the peptides to a wall on the C-terminal and using a process called Edman Degradation to remove an amino acid from the N-Terminal. Even though a framework (Whatprot) has been proposed for the peptide classification task, processing times remain restrictive due to the massively parallel data acquisicion system. In this paper, we propose a new beam search decoder with a novel state formulation that obtains considerably lower processing times at the expense of only a slight accuracy drop compared to Whatprot. Furthermore, we explore how our novel state formulation may lead to even faster decoders in the future. Author summary: Proteomic analyses frequently rely on mass spectrometry, a method characterized by its limited dynamic range, potentially overlooking low-abundant proteins. To address this limitation, single-molecule protein sequencing methods offer a solution. Fluorosequencing is a cutting-edge single-molecule protein sequencing method, which can distinguish peptides or protein molecules massively parallelly. This method has attracted interest from investors, as evidenced by the recent funding of Erisyon, a company developing this technology. This technique contains a challenging classification task: determining the original peptide sequence from light-intensity observations obtained after several Edman cycles. A classifier based on a combination of k Nearest Neighbors (kNN) with Hidden Markov Models (HMM) had been shown to have close-to-optimal accuracy with tractable complexity. We propose in this paper a new algorithm that reduces computation time significantly at the expense of a slight reduction in accuracy compared to state-of-the-art method. [ABSTRACT FROM AUTHOR]

This paper proposes a new paradigm for the biophysical concept of measuring the affinity of molecular complexes, based on a matrix representation of biological interactions and subsequent numerical analysis of the stability of this matrix. Our numerical criterion of stability (lg(cond(W))) correlates well with experimental values such as K d and IC 5 0 as well as with experimental data of aggregation kinetics in studies of amyloid peptides. The main goal of this work is to reduce the cost of biochemical experiments by obtaining preliminary information on the interaction of chemical compounds. The paper also presents our numerical calculations in comparison with a large amount of experimental data on the examples of binding of small chemical molecules gefitinib, erlotinib, imatinib, naquatinib, and CO-1686 with proteins, protein–peptide interactions of the Bcl-2 protein family, antibody–antigen CD20–rituximab, and aggregation of amyloid peptides. The description of the software package that implements the presented algorithm is given on the website: https://binomlabs.com/. [ABSTRACT FROM AUTHOR]

In recent years, heavy metal pollution has become increasingly prominent, severely damaging ecosystems and biodiversity, and posing a serious threat to human health. However, the results of current methods for heavy metal restoration are not satisfactory, so it is urgent to find a new and effective method. Peptides are the units that make up proteins, with small molecular weights and strong biological activities. They can effectively repair proteins by forming complexes, reducing heavy metal ions, activating the plant's antioxidant defense system, and promoting the growth and metabolism of microorganisms. Peptides show great potential for the remediation of heavy metal contamination due to their special structure and properties. This paper reviews the research progress in recent years on the use of peptides to remediate heavy metal pollution, describes the mechanisms and applications of remediation, and provides references for the remediation of heavy metal pollution. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome corona virus 2 (SARS CoV-2) is the cause of Corona virus disease 2019 (COVID-19), which turned into a pandemic in late 2019 and early 2020. SARS CoV-2 causes endothelial cell destruction and swelling, microthrombosis, constriction of capillaries, and malfunction of pericytes, all of which are detrimental to capillary integrity, angiogenesis, and healing processes. Cytokine storming has been connected to COVID-19 disease. Hypoxemia and tissue hypoxia may arise from impaired oxygen diffusion exchange in the lungs due to capillary damage and congestion. This personal view will look at how inflammation and capillary damage affect blood and tissue oxygenation, cognitive function, and the duration and intensity of COVID-19 disease. The general effects of microvascular injury, hypoxia, and capillary damage caused by COVID-19 in key organs are also covered in this point of view. Once initiated, this vicious cycle leads to diminished capillary function, which exacerbates inflammation and tissue damage, and increased inflammation due to hypoxia. Brain damage may result from low oxygen levels and high cytokines in brain tissue. In this paper we give a summary in this direction with focus on the role of the neuropeptide Substance P. On the basis of this, we discuss selected approaches to the question: "How Substance P is involved in the etiology of the COVID-19 and how results of our research could improve the prevention or therapy of corona? Thereby pointing out the role of Substance P in the postcorona syndrome and providing novel concepts for therapy and prevention. [ABSTRACT FROM AUTHOR]

This paper presents the initial exploration of the free radical scavenging capabilities of peptides derived from protein hydrolysates (PPH) obtained from Zingiber cassumunar rhizomes (Phlai). To replicate the conditions of gastrointestinal digestion, a combination of pepsin and pancreatin proteolysis was employed to generate these hydrolysates. Subsequently, the hydrolysate underwent fractionation using molecular weight cut-off membranes at 10, 5, 3, and 0.65 kDa. The fraction with a molecular weight less than 0.65 kDa exhibited the highest levels ABTS, DPPH, FRAP, and NO radical scavenging activity. Following this, RP-HPLC was used to further separate the fraction with a molecular weight less than 0.65 kDa into three sub-fractions. Among these, the F5 sub-fraction displayed the most prominent radical-scavenging properties. De novo peptide sequencing via quadrupole-time-of-flight-electron spin induction-mass spectrometry identified a pair of novel peptides: Asp-Gly-Ile-Phe-Val-Leu-Asn-Tyr (DGIFVLNY or DY-8) and Ile-Pro-Thr-Asp-Glu-Lys (IPTDEK or IK-6). Database analysis confirmed various properties, including biological activity, toxicity, hydrophilicity, solubility, and potential allergy concerns. Furthermore, when tested on the human adenocarcinoma colon (Caco-2) cell line, two synthetic peptides demonstrated cellular antioxidant activity in a concentration-dependent manner. These peptides were also assessed using the FITC Annexin V apoptosis detection kit with PI, confirming the induction of apoptosis. Notably, the DY-8 peptide induced apoptosis, upregulated mRNA levels of caspase-3, -8, and -9, and downregulated Bcl-2, as confirmed by real-time quantitative polymerase chain reaction (RT-qPCR). Western blot analysis indicated increased pro-apoptotic Bax expression and decreased anti-apoptotic Bcl-2 expression in Caco-2 cells exposed to the DY-8 peptide. Molecular docking analysis revealed that the DY-8 peptide exhibited binding affinity with Bcl-2, Bcl-xL, and Mcl-1, suggesting potential utility in combating colon cancer as functional food ingredients. [ABSTRACT FROM AUTHOR]

This concept paper elucidates the possible influence of the electrical double layer (EDL) and the polyelectrolytic nature of bacterial cell walls on the behavior of antimicrobial peptides (AMPs) and lipopeptides. It proposes that the presence of EDL adjacent to lipid membranes may play a crucial role in inducing peptide aggregation and conformational changes, thus affecting their antimicrobial activity. Furthermore, it emphasizes that the negatively charged components in both Gram‐positive and Gram‐negative bacterial cell walls may act as polyelectrolytes, effectively reducing the critical micellization concentration (CMC) of positively charged peptides and lipopeptides. This reduction is expected to facilitate their aggregation, potentially enhancing their accumulation at the bacterial membrane and increasing their effectiveness in disrupting membrane integrity and exerting antimicrobial activity. Therefore, understanding the interplay between EDL effects, polyelectrolytic properties of bacterial cell walls, and the behavior of antimicrobial peptides is essential for elucidating their mechanisms of action and optimizing their therapeutic potential. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance, particularly the emergence of resistant strains in fungal pathogens, has become a pressing global health concern. Antifungal peptides (AFPs) have shown great potential as a promising alternative therapeutic strategy due to their inherent antimicrobial properties and potential application in combating fungal infections. However, the identification of antifungal peptides using experimental approaches is time-consuming and costly. Hence, there is a demand to propose fast and accurate computational approaches to identifying AFPs. This paper introduces a novel multi-view feature learning (MVFL) model, called AFP-MVFL, for accurate AFP identification, utilizing multi-view feature learning. By integrating the sequential and physicochemical properties of amino acids and employing a multi-view approach, the AFP-MVFL model significantly enhances prediction accuracy. It achieves 97.9%, 98.4%, 0.98, and 0.96 in terms of accuracy, precision, F1 score, and Matthews correlation coefficient (MCC), respectively, outperforming previous studies found in the literature. [ABSTRACT FROM AUTHOR]

According to data from the World Health Organization (WHO), cancer is considered to be one of the leading causes of death worldwide, and new therapeutic approaches, especially improved novel cancer treatment regimens, are in high demand. Considering that many chemotherapeutic drugs tend to have poor pharmacokinetic profiles, including rapid clearance and limited on-site accumulation, a combined approach with tumor-homing peptide (THP)-functionalized magnetic nanoparticles could lead to remarkable improvements. This is confirmed by an increasing number of papers in this field, showing that the on-target peptide functionalization of magnetic nanoparticles improves their penetration properties and ensures tumor-specific binding, which results in an increased clinical response. This review aims to highlight the potential applications of THPs in combination with magnetic carriers across various fields, including a pharmacoeconomic perspective. [ABSTRACT FROM AUTHOR]

Peptides, both natural and synthetic, are well suited for a wide range of purposes and offer versatile applications in different fields such as biocatalysts, injectable hydrogels, tumor treatment, and drug delivery. The research of the better part of the cited papers was conducted using various database platforms such as MetalPDB. The rising prominence of therapeutic peptides encompasses anticancer, antiviral, antimicrobial, and anti-neurodegenerative properties. The metals Na, K, Mg, Ca, Fe, Mn, Co, Cu, Zn, and Mo are ten of the twenty elements that are considered essential for life. Crucial for understanding the biological role of metals is the exploration of metal-bound proteins and peptides. Aside from essential metals, there are other non-essential metals that also interact biologically, exhibiting either therapeutic or toxic effects. Irregularities in metal binding contribute to diseases like Alzheimer's, neurodegenerative disorders, Wilson's, and Menkes disease. Certain metal complexes have potential applications as radiopharmaceuticals. The examination of these complexes was achieved by preforming UV–Vis, IR, EPR, NMR spectroscopy, and X-ray analysis. This summary, although unable to cover all of the studies in the field, offers a review of the ongoing experimentation and is a basis for new ideas, as well as strategies to explore and gain knowledge from the extensive realm of peptide-chelated metals and biotechnologies. [ABSTRACT FROM AUTHOR]

During their biosynthesis, Sonic hedgehog (Shh) morphogens are covalently modified by cholesterol at the C-terminus and palmitate at the N-terminus. Although both lipids initially anchor Shh to the plasma membrane of producing cells, it later translocates to the extracellular compartment to direct developmental fates in cells expressing the Patched (Ptch) receptor. Possible release mechanisms for dually lipidated Hh/Shh into the extracellular compartment are currently under intense debate. In this paper, we describe the serum-dependent conversion of the dually lipidated cellular precursor into a soluble cholesteroylated variant (ShhC) during its release. Although ShhC is formed in a Dispatched- and Scube2-dependent manner, suggesting the physiological relevance of the protein, the depalmitoylation of ShhC during release is inconsistent with the previously postulated function of N-palmitate in Ptch receptor binding and signaling. Therefore, we analyzed the potency of ShhC to induce Ptch-controlled target cell transcription and differentiation in Hh-sensitive reporter cells and in the Drosophila eye. In both experimental systems, we found that ShhC was highly bioactive despite the absence of the N-palmitate. We also found that the artificial removal of N-terminal peptides longer than eight amino acids inactivated the depalmitoylated soluble proteins in vitro and in the developing Drosophila eye. These results demonstrate that N-depalmitoylated ShhC requires an N-peptide of a defined minimum length for its signaling function to Ptch. [ABSTRACT FROM AUTHOR]

Endogenous peptides, particularly those with post-translational modifications, are increasingly being studied as biomarkers for diagnosing various diseases. However, they are weakly ionizable, have a low abundance in biological samples, and may be interfered with by high levels of proteins, peptides, and other macromolecular impurities, resulting in a high limit of detection and insufficient amounts of post-translationally modified peptides in real biological samples to be examined. Therefore, separation and enrichment are necessary before analyzing these biomarkers using mass spectrometry. Mesoporous materials have regular adjustable pores that can eliminate large proteins and impurities, and their large specific surface area can bind more target peptides, but this may result in the partial loss or destruction of target peptides during centrifugal separation. On the other hand, magnetic mesoporous materials can be used to separate the target using an external magnetic field, which improves the separation efficiency and yield. Core–shell magnetic mesoporous materials are widely utilized for peptide separation and enrichment due to their biocompatibility, efficient enrichment capability, and excellent recoverability. This paper provides a review of the latest progress in core–shell magnetic mesoporous materials for enriching glycopeptides and phosphopeptides and compares their enrichment performance with different types of functionalization methods. [ABSTRACT FROM AUTHOR]

Honey is a natural product that is used by a large number of people because of its distinctive compositional constituents, which have a considerable impact on its market value. The distinctive combination of amino acids and sugars found in honey's composition, along with its peptide content, could potentially provide several benefits to human health. During the past few years, cutting-edge techniques have been developed and used for the purpose of investigating, identifying, and characterizing peptides that are produced from honey bees. Therefore, the purpose of this review is to examine current trends and technological advancements in the study of honey bee-derived peptides, focusing on innovative and cutting-edge methods. Furthermore, this review explores various attributes of honey and its components, including the honey bee-derived peptide defensin-1. In addition, this review investigates various methods for separating and purifying peptides, as well as the factors that affect these methods. Additionally, defensin-1, a peptide produced by honey bees, is discussed along with its antioxidant and antimicrobial capabilities. In addition, this review focuses on cutting-edge and innovative omic methods used to study honey bee peptides, as well as the significance of artificial intelligence tools in their investigation. Consequently, the review paper delves into various significant obstacles faced by researchers and scientists studying honey bee peptides, while also offering an extensive range of fascinating opportunities and possibilities for future research for those interested in groundbreaking discoveries in this area. [ABSTRACT FROM AUTHOR]

Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties, putting them on a new path in medicine. Their conformational rigidity improves proteolytic stability and leads to rapid penetration into tissues via any possible route of administration. Moreover, elimination of renal metabolism is of great importance, for example, for people with a history of liver diseases. In addition, each ring can function independently, making bicyclic peptides extremely versatile molecules for further optimization. In this paper, we compared the potentiometric and spectroscopic properties studied by UV–vis, MCD, and EPR of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH) (BCL). In particular, we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL1 (Ac-PKKHPc(CFWKTC)PKKH-NH2) that contains the unbinding cycle and N- and C-terminal linear parts with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position, i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH2) and in the C-terminal position, i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH2), respectively; and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH2). Potentiometric results have shown that the bicyclic structure promotes the involvement of the side chain imidazole donors in Cu(II) binding. On the other hand, the results obtained for the mono-cyclic analogues lead to the conclusion that the coordination of the histidine moiety as an anchoring group is promoted by its location in the peptide sequence further from the nonbinding cycle, strongly influencing the involvement of the amide donors in Cu(II) coordination. [ABSTRACT FROM AUTHOR]

In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer Metastasis has been mostly misunderstood and underestimated by the general public regarding cancer deaths. The aims and objectives of the present report was to more fully describe the scientific activities and components that are involved in the malignant cell's fulfillment of the metastatic process and to impress the readership that metastasis is the major cause on all cancer deaths. The paper proceeds to enumerate and describe certain factors that contribute to cancer cell proliferation and subsequent metastasis such as; (a) calcium levels, (b) multiple cell membrane channels, and (c) the chemokine/receptor system. These latter components could serve to provide ideal molecular targets for possible future peptide therapeutic applications in treating cancer patients. Metastasis (Met) largely contributes to the major cause of cancer deaths throughout the world, rather than the growth of the tumor mass itself. The present report brings together several of the pertinent contributors to cancer growth and metastatic processes from an activity standpoint. Such biological activities include the following: (1) cell adherence and detachment; (2) cell-to-cell contact; (3) contact inhibition; (4) the cell interfacing with the extracellular matrix (ECM); (5) tumor cell-to-stroma communication networks; (6) chemotaxis; and (7) cell membrane potential. Moreover, additional biochemical factors that contribute to cancer growth and metastasis have been shown to comprise the following: (a) calcium levels in the extracellular matrix and in intracellular compartments; (b) cation voltage and ATP-regulated potassium channels; (c) selective and non-selective cation channels; and (d) chemokines (cytokines) and their receptors, such as CXCL12 (SDF-1) and its receptor/binding partner, CXCR4. These latter molecular components represent a promising group of an interacting and synchronized set of candidates ideal for peptide therapeutic targeting for cancer growth and metastasis. Such peptides can be obtained from naturally occurring proteins such as alpha-fetoprotein (AFP), an onco-fetal protein and clinical biomarker. [ABSTRACT FROM AUTHOR]

The rapid development of vaccines is a crucial objective in modern biotechnology and molecular pharmacology. In this context, conducting research to expedite the selection of a potent immunogen is imperative. The candidate vaccine should induce the production of antibodies that can recognize the immunogenic epitopes of the target protein, resembling the ones found in recovered patients. One major challenge in vaccine development is the absence of straightforward and reliable techniques to determine the extent to which the spectrum of antibodies produced after vaccination corresponds to antibodies found after recovery. This paper describes a newly developed method to detect antibodies specific to immunogenic epitopes of the target protein in blood plasma and to compare them with antibody spectra generated post vaccination. Comparing the antibody pool generated in the human body after recovering from an infectious disease with the pool formed through vaccination can become a universal method for screening candidate vaccines. This method will enable the identification of candidate vaccines that can induce the production of antibodies similar to those generated in response to a natural infection. Implementing this approach will facilitate the rapid development of new vaccines, even when faced with a pandemic. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is a major cause of heart failure. The carboxypeptidase cathepsin A is a novel target in the treatment of cardiac failure. We aim to show that recently developed inhibitors of the protease cathepsin A attenuate post-MI heart failure.Methods: Mice were subjected to permanent left anterior descending artery (LAD) ligation or sham operation. 24 h post-surgery, LAD-ligated animals were treated with daily doses of the cathepsin A inhibitor SAR1 or placebo. After 4 weeks, the three groups (sham, MI-placebo, MI-SAR1) were evaluated.Results: Compared to sham-operated animals, placebo-treated mice showed significantly impaired cardiac function and increased plasma BNP levels. Cathepsin A inhibition prevented the increase of plasma BNP levels and displayed a trend towards improved cardiac functionality. Proteomic profiling was performed for the three groups (sham, MI-placebo, MI-SAR1). More than 100 proteins were significantly altered in placebo-treated LAD ligation compared to the sham operation, including known markers of cardiac failure as well as extracellular/matricellular proteins. This ensemble constitutes a proteome fingerprint of myocardial infarction induced by LAD ligation in mice. Cathepsin A inhibitor treatment normalized the marked increase of the muscle stress marker CA3 as well as of Igγ 2b and fatty acid synthase. For numerous further proteins, cathepsin A inhibition partially dampened the LAD ligation-induced proteome alterations.Conclusions: Our proteomic and functional data suggest that cathepsin A inhibition has cardioprotective properties and support a beneficial effect of cathepsin A inhibition in the treatment of heart failure after myocardial infarction. [ABSTRACT FROM AUTHOR]

We have previously shown that ethanolic extract from bark (EEB) ofSalix aegyptiaca(Musk Willow) can inhibit proliferation and motility and induce apoptosis in colon cancer cells. Tandem mass spectrometry revealed EEB to be rich in catechin, catechol, and salicin. The present study investigated the chemopreventive effect of HPLC-fingerprinted EEB on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) formation in mice. DMH (20 mg/kg body weight) was weekly injected subcutaneously to mice for the first 2 weeks. EEB (100 and 400 mg/kg body weight) was provided orally from the 7th to 14th week, after which colon tissues were evaluated histologically and biochemically. DMH treatment induced high number of ACF; EEB significantly reduced the number and multiplicity of ACF, along with a restoration in goblet cells and mucin accumulation. EEB supplementation improved the markers of inflammation (myeloperoxidase and neutrophil infiltration) and oxidative stress. More importantly, EEB amplified apoptosis of neoplastic cells in the colon mucosa of DMH-treated mice. It also lowered levels of markers for early transformation events such as EGFR, nuclear β-catenin, and COX-2 in colon cancer cell lines HT-29 and HCT-116. The innocuity of EEB (up to 1600 mg/kg) to mice reinforces its potential as a chemopreventive agent. [ABSTRACT FROM AUTHOR]

In this paper, we report an open system consisting of three self-replicating peptides, in which peptide 1 inhibits the duplex template of peptide 2, peptide 2 inhibits duplex 3, and peptide 3 inhibits duplex 1 to complete the negative feedback loop. This interacting chemical network yields oscillations in the concentrations of all species over time and establishes a possible mechanism for pre-biotic chemical systems organization. The first focus of our analysis is the effect of altering rates of duplex formation and inhibition on oscillations. We then examine the autocatalytic rate constant in the symmetric and asymmetric cases. [ABSTRACT FROM AUTHOR]

The fire protection of materials has an important role in our everyday life and covers a highly diverse spectrum of substances, materials, and fields of application. Important fields of application for fire protection, especially in public areas, are construction and transport, electronic devices, furnishings, and textiles (e.g., applications for occupational safety, carpets, curtains, upholstery, insulation, and technical applications in outdoor areas). The efficient and durable finishing of materials with flame retardant additives is crucial to ensure effective fire protection. Many of the flame retardant additives currently used are based on bromides, chlorides, phosphates, or antimony. However, these flame retardants are harmful to the environment and/or health (not phosphates). Therefore, the use of these flame retardants is already being restricted by EU directives (e.g., REACH regulation), and it is foreseeable that they will be further restricted in the future. To keep up with this development, innovative and sustainable solutions must be developed in the short term. The amount of flame retardant additives that are harmful to the environment and health must be reduced. In the medium term, these harmful additives must be completely replaced by sustainable flame retardant additives that are not harmful to the environment and health. This paper describes research results to reduce the amount of additives in the short term. In order to reduce the amount of additives used, an innovative refinement process is being developed. In a first step, the flame retardant additives are combined with bio-based adhesion promoters (anchor peptides). Anchor peptides bind with high selectivity, binding strength, and occupancy density to a broad portfolio of materials (e.g., synthetic polymers, metals, ceramics, and natural materials) and enable the finishing of the materials with a broad spectrum of functional units (e.g., flame retardant additives). Material functionalization by anchor peptides is energy-efficient and resource-saving at room temperature in aqueous solution and is scalable in its production. Based on these developments, in this paper, a finishing process is presented with which flame retardant textiles can be equipped with bio-based anchor peptides. A requirements' outline for the new finishing process is described. Established processes (e.g., foulard, coating machine, and roller application) are compared with each other and evaluated with regard to the requirements and their suitability. The most suitable process is then designed, and a laboratory scale as well as an industry scale concept are presented. [ABSTRACT FROM AUTHOR]

Cell-adhesive factors mediate adhesion of cells to substrates via peptide motifs such as the Arg–Gly–Asp (RGD) sequence. With the onset of sustainability issues, there is a pressing need to find alternatives to animal-derived cell-adhesive factors, especially for cell-cultivated food applications. In this paper, we show how data mining can be a powerful approach toward identifying fungal-derived cell-adhesive proteins and present a method to isolate and utilize these proteins as extracellular matrices (ECM) to support cell adhesion and culture in 3D. Screening of a protein database for fungal and plant proteins uncovered that ~5.5% of the unique reported proteins contain RGD sequences. A plot of fungi species vs RGD percentage revealed that 98% of the species exhibited an RGD percentage > = 1%. We observed the formation of protein particles in crude extracts isolated from basidiomycete fungi, which could be correlated to their stability towards particle aggregation at different temperatures. These protein particles were incorporated in 3D fiber matrices encapsulating mouse myoblast cells, showing a positive effect on cell alignment. We demonstrated a cell traction stress on the protein particles (from Flammulina velutipes) that was comparable to cells on fibronectin. A snapshot of the RGD-containing proteins in the fungal extracts was obtained by combining SDS-PAGE and mass spectrometry of the peptide fragments obtained by enzymatic cleavage. Therefore, a sustainable source of cell-adhesive proteins is widely available in the fungi kingdom. A method has been developed to identify candidate species and produce cell-adhesive matrices, applicable to the cell-cultivated food and healthcare industries. [ABSTRACT FROM AUTHOR]

Keywords: bariatric surgery; mass spectrometry; peptide YY EN bariatric surgery mass spectrometry peptide YY 763 765 3 05/05/23 20230601 NES 230601 We note that Maurer et al., in their correspondence,[1] have raised some concerns about the preanalytical and analytical validation of the peptide YY (PYY) assay described in our paper 'The postprandial secretion of peptide YY SB 1 sb SB -36 sb and SB 3 sb SB -36 sb in obesity is differentially increased after gastric bypass versus sleeve gastrectomy'.[2] The validation and assay characteristics were not the primary objectives of the paper. We have studied the stability of both PYY species with our inhibitor mix containing DPP4 inhibitor and Aprotinin, where we spiked PYY SB 1 sb SB -36 sb and PYY SB 3 sb SB -36 sb into plasma EDTA and LH from three different volunteers. [Extracted from the article]

Background: Viral infections have been the main health issue in the last decade. Antiviral peptides (AVPs) are a subclass of antimicrobial peptides (AMPs) with substantial potential to protect the human body against various viral diseases. However, there has been significant production of antiviral vaccines and medications. Recently, the development of AVPs as an antiviral agent suggests an effective way to treat virus-affected cells. Recently, the involvement of intelligent machine learning techniques for developing peptide-based therapeutic agents is becoming an increasing interest due to its significant outcomes. The existing wet-laboratory-based drugs are expensive, time-consuming, and cannot effectively perform in screening and predicting the targeted motif of antiviral peptides. Methods: In this paper, we proposed a novel computational model called Deepstacked-AVPs to discriminate AVPs accurately. The training sequences are numerically encoded using a novel Tri-segmentation-based position-specific scoring matrix (PSSM-TS) and word2vec-based semantic features. Composition/Transition/Distribution-Transition (CTDT) is also employed to represent the physiochemical properties based on structural features. Apart from these, the fused vector is formed using PSSM-TS features, semantic information, and CTDT descriptors to compensate for the limitations of single encoding methods. Information gain (IG) is applied to choose the optimal feature set. The selected features are trained using a stacked-ensemble classifier. Results: The proposed Deepstacked-AVPs model achieved a predictive accuracy of 96.60%%, an area under the curve (AUC) of 0.98, and a precision-recall (PR) value of 0.97 using training samples. In the case of the independent samples, our model obtained an accuracy of 95.15%, an AUC of 0.97, and a PR value of 0.97. Conclusion: Our Deepstacked-AVPs model outperformed existing models with a ~ 4% and ~ 2% higher accuracy using training and independent samples, respectively. The reliability and efficacy of the proposed Deepstacked-AVPs model make it a valuable tool for scientists and may perform a beneficial role in pharmaceutical design and research academia. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area. [ABSTRACT FROM AUTHOR]

Simple Summary: This review mainly focuses on epigenetic changes in a few selective genes associated with insulin insensitivity in the periphery and how this peripheral insulin insensitivity is linked with impaired signaling of insulin in the brain, thus causing Alzheimer's disease. DNA methylation and histone modifications are the focus of this review, with primary importance given to DNA methylation. Moreover, there has been a focus shift from the amyloid β hypothesis to epigenetic mechanisms. Furthermore, we discuss the advanced drug delivery systems that can be used for the delivery of drugs targeting the brain during Alzheimer's disease. The advanced drug delivery systems discussed in this paper are nanoparticles, vesicular systems, network systems and dendrimers, hydrogel-based systems, and biologics. Alzheimer's disease (AD) is a neurodegenerative condition that predominantly affects the hippocampus and the entorhinal complex, leading to memory lapse and cognitive impairment. This can have a negative impact on an individual's behavior, speech, and ability to navigate their surroundings. AD is one of the principal causes of dementia. One of the most accepted theories in AD, the amyloid β (Aβ) hypothesis, assumes that the buildup of the peptide Aβ is the root cause of AD. Impaired insulin signaling in the periphery and central nervous system has been considered to have an effect on the pathophysiology of AD. Further, researchers have shifted their focus to epigenetic mechanisms that are responsible for dysregulating major biochemical pathways and intracellular signaling processes responsible for directly or indirectly causing AD. The prime epigenetic mechanisms encompass DNA methylation, histone modifications, and non-coding RNA, and are majorly responsible for impairing insulin signaling both centrally and peripherally, thus leading to AD. In this review, we provide insights into the major epigenetic mechanisms involved in causing AD, such as DNA methylation and histone deacetylation. We decipher how the mechanisms alter peripheral insulin signaling and brain insulin signaling, leading to AD pathophysiology. In addition, this review also discusses the need for newer drug delivery systems for the targeted delivery of epigenetic drugs and explores targeted drug delivery systems such as nanoparticles, vesicular systems, networks, and other nano formulations in AD. Further, this review also sheds light on the future approaches used for epigenetic drug delivery. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs), commonly referred to as host defense peptides, are found in a wide range of organisms, including bacteria, plants, and both vertebrate and invertebrate animals. They function as an initial defense mechanism against pathogenic microorganisms, modulate immune responses, and in specific instances, confer protection against the onset of cancer. Pleurocidin (Ple) is a linear antimicrobial peptide with amphipathic a-helical conformation, isolated originally from the winter flounder (Pleuronectes americanus), notable for its wide-ranging effectiveness against both bacteria and fungi. While the majority of research on pleurocidin's biological characteristics has primarily focused on deciphering its mechanisms of interaction with the biological membranes of pathogenic bacteria and host cells, as well as investigating its modes of killing activities, there is a growing body of evidence suggesting that pleurocidin and pleurocidin-derived analogs might be effectively employed as anti-cancer agents against breast carcinoma and leukemia due to their potent cytotoxic properties and selectivity towards cancer cells. Notably, some characteristics of pleurocidin observed in microbiological investigations of this compound could be effectively applied in examining the anti-cancer capabilities of Ple-like derivatives. This review provides a comprehensive overview of the literature on the biological activities of pleurocidin, pleurocidin-derived peptides, pleurocidin-containing hybrid peptides, and nanosystems. The primary emphasis is on elucidating the range of activities exhibited by these compounds, evaluating their potential therapeutic applications, assessing their safety profile, and identifying any limits observed thus far. This paper will also discuss potential areas for further investigation into the anti-cancer effects of Ple and its derivatives, drawing insights from microbiological research. [ABSTRACT FROM AUTHOR]

Effective drug delivery is essential for cancer treatment. Drug delivery systems, which can be tailored to targeted transport and integrated tumor therapy, are vital in improving the efficiency of cancer treatment. Peptides play a significant role in various biological and physiological functions and offer high design flexibility, excellent biocompatibility, adjustable morphology, and biodegradability, making them promising candidates for drug delivery. This paper reviews peptide-mediated drug delivery systems, focusing on self-assembled peptides and peptide–drug conjugates. It discusses the mechanisms and structural control of self-assembled peptides, the varieties and roles of peptide–drug conjugates, and strategies to augment peptide stability. The review concludes by addressing challenges and future directions. [ABSTRACT FROM AUTHOR]

Chagas disease and leishmaniasis are both neglected tropical diseases that affect millions of people around the world. Leishmaniasis is currently the second most widespread vector-borne parasitic disease after malaria. The World Health Organization records approximately 0.7–1 million newly diagnosed leishmaniasis cases each year, resulting in approximately 20,000–30,000 deaths. Also, 25 million people worldwide are at risk of Chagas disease and an estimated 6 million people are infected with Trypanosoma cruzi. Pentavalent antimonials, amphotericin B, miltefosine, paromomycin, and pentamidine are currently used to treat leishmaniasis. Also, nifurtimox and benznidazole are two drugs currently used to treat Chagas disease. These drugs are associated with toxicity problems such as nephrotoxicity and cardiotoxicity, in addition to resistance problems. As a result, the discovery of novel therapeutic agents has emerged as a top priority and a promising alternative. Overall, there is a need for new and effective treatments for Chagas disease and leishmaniasis, as the current drugs have significant limitations. Peptide-based drugs are attractive due to their high selectiveness, effectiveness, low toxicity, and ease of production. This paper reviews the potential use of peptides in the treatment of Chagas disease and leishmaniasis. Several studies have demonstrated that peptides are effective against Chagas disease and leishmaniasis, suggesting their use in drug therapy for these diseases. Overall, peptides have the potential to be effective therapeutic agents against Chagas disease and leishmaniasis, but more research is needed to fully investigate their potential. [ABSTRACT FROM AUTHOR]

α-Amylase inhibitory peptides are used to treat diabetes, but few studies have statistically characterized their interaction with α-amylase. This study performed the molecular docking of α-amylase with inhibitory peptides from published papers. The key sites, side chain chargeability, and hydrogen bond distribution characteristics were analyzed. Molecular dynamics simulated the role of key sites in complex stability. Moreover, partial least squares regression (PLSR) was used to analyze the contribution of different amino acids in the peptides to inhibition. The results showed that, for the α-amylase molecule, His201 and Gln63, with the highest interaction numbers (INs, 15, 15) and hydrogen bond values (HBVs, 11.50, 10.33), are the key sites on α-amylase, and amino acids with positively charged side chains were important for inhibitory activity. For the inhibitory peptides, Asp and Arg had the highest HBVs, and amino acids with charged side chains were more likely to form hydrogen bonds and exert inhibitory activity. In molecular dynamics simulations, peptides involving key binding sites formed more stable complexes with α-amylase than α-amylase alone, suggesting enhanced inhibitory effects. Further, PLSR results showed that amino acids close to the N-terminus of the inhibitory peptide, located in the third and fifth positions, were significantly correlated with its inhibitory activity. In conclusion, this study provides a new approach to developing and screening α-amylase inhibitors. [ABSTRACT FROM AUTHOR]

The process of oxidation is believed to be mainly responsible for different chronic diseases and the deterioration of food by reducing shelf life. Antioxidants are known to scavenge various free radicals like hydroxyl radicals, and peroxyl radicals, and also inhibit lipid peroxidation. An increasing number of peptides and hydrolysates possessing antioxidant capacity have been characterized by soybean and other soy-based products. Due to their high protein content, soybeans, and other soy products are considered to be a great source for generating antioxidative peptides using enzymatic hydrolysis or microbial fermentation. This paper focuses on the recent advances in soy-derived antioxidative peptides, especially the methods for producing the peptides, evaluating the antioxidant capacity in vitro and in vivo, and purifying and identifying the most active peptide fraction and the factors influencing their antioxidant activity. • Soybean and soy-based products hold significant potential as rich sources of antioxidative peptides. • This paper provides a comprehensive summary of bioactive peptides, with a particular focus on those derived from soybean. • The review explores the structure-activity relationship of soybean peptides, shedding light on their functional properties. • Further research is necessary to explore and optimize the utilization of these bioactive peptides for various applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Bovine IgG1 Fc receptor (boFcγRIII) is a homologue to human FcγRIII (CD16) that has two extracellular Ig-like domains and can bind bovine IgG1 with medium–low affinity. We identified the Fc-binding site as well as its key residues for IgG1 binding using synthetic peptides, which is located in the second extracellular domain of boFcγRIII. It provides new insights for the IgG–Fcγ interaction and FcγR-targeting drugs development. The bovine IgG1 Fc receptor (boFcγRIII) is a homologue to human FcγRIII (CD16) that binds bovine IgGI with medium–low affinity. In order to identify the Fc-binding site on the bovine IgG1 Fc receptor (boFcγRIII), peptides derived from the second extracellular domain (EC2) of boFcγRIII were synthesized and conjugated with the carrier protein. With a Dot-blot assay, the ability of the peptides to bind bovine IgG1 was determined, and the IgG1-binding peptide was also identified via truncation and mutation. The minimal peptide AQRVVN corresponding to the sequence 98–103 of boFcγRIII bound bovine IgG1 in Dot-blot, suggesting that it represents a linear ligand-binding site located in the putative A–B loop of the boFcγRIII EC2 domain. Mutation analysis of the peptide showed that the residues of Ala98, Gln99, Val101, Val102 and Asn103 within the Fc-binding site are critical for IgG1 binding on boFcγRIII. The functional peptide identified in this paper is of great value to the IgG–Fc interaction study and FcR-targeting drug development. [ABSTRACT FROM AUTHOR]

Leptin is a tonic appetite-regulating hormone, which is integral for the long-term regulation of energy balance. The current evidence suggests that the typical orexigenic or anorexigenic response of many of these appetite-regulating hormones, most notably ghrelin and cholecystokinin (CCK), require leptin to function whereas glucagon-like peptide-1 (GLP-1) is required for leptin to function, and these responses are altered when leptin injection or gene therapy is administered in combination with these same hormones or respective agonists. The appetite-regulatory pathway is complex, thus peptide tyrosine tyrosine (PYY), brain-derived neurotrophic factor (BDNF), orexin-A (OXA), and amylin also maintain ties to leptin, however these are less well understood. While reviews to date have focused on the existing relationships between leptin and the various neuropeptide modulators of appetite within the central nervous system (CNS) or it's role in thermogenesis, no review paper has synthesised the information regarding the interactions between appetite-regulating hormones and how leptin as a chronic regulator of energy balance can influence the acute appetite-regulatory response. Current evidence suggests that potential relationships exist between leptin and the circulating peripheral appetite hormones ghrelin, GLP-1, CCK, OXA and amylin to exhibit either synergistic or opposing effects on appetite inhibition. Though more research is warranted, leptin appears to be integral in both energy intake and energy expenditure. More specifically, functional leptin receptors appear to play an essential role in these processes. [ABSTRACT FROM AUTHOR]

Most of the active proteins and industrial enzymes commonly used in industry, agriculture and medicine are obtained through heterologous expression systems. Pichia pastoris is one of the excellent hosts for expressing heterologous proteins. This expression system has the advantages including good genetic stability, high protein expression and secretory level, post-translational modification system, and low cost etc. However, excessive aggregation of heterologous proteins usually leads to incorrect fold and ineffective secretion of the target proteins, thus decling protein expression level. This paper reviewed the progress in the study on exogenous protein expression in Pichia pastoris by engineering the secretion and folding pathways such as signal peptide optimization, chaperone optimization and fusion protein expression. [ABSTRACT FROM AUTHOR]

Synapse loss is the principal cause of cognitive decline in Alzheimer's disease (AD) and related disorders (ADRD). Synapse development depends on the intricate dynamics of the neuronal cytoskeleton. Cofilin, the major protein regulating actin dynamics, can be sequestered into cofilactin rods, intra-neurite bundles of cofilin-saturated actin filaments that can disrupt vesicular trafficking and cause synaptic loss. Rods are a brain pathology in human AD and mouse models of AD and ADRD. Eliminating rods is the focus of this paper. One pathway for rod formation is triggered in ~20% of rodent hippocampal neurons by disease-related factors (e.g., soluble oligomers of Amyloid-β (Aβ)) and requires cellular prion protein (PrPC), active NADPH oxidase (NOX), and cytokine/chemokine receptors (CCRs). FDA-approved antagonists of CXCR4 and CCR5 inhibit Aβ-induced rods in both rodent and human neurons with effective concentrations for 50% rod reduction (EC50) of 1–10 nM. Remarkably, two D-amino acid receptor-active peptides (RAP-103 and RAP-310) inhibit Aβ-induced rods with an EC50 of ~1 pM in mouse neurons and ~0.1 pM in human neurons. These peptides are analogs of D-Ala-Peptide T-Amide (DAPTA) and share a pentapeptide sequence (TTNYT) antagonistic to several CCR-dependent responses. RAP-103 does not inhibit neuritogenesis or outgrowth even at 1 µM, >106-fold above its EC50. N-terminal methylation, or D-Thr to D-Ser substitution, decreases the rod-inhibiting potency of RAP-103 by 103-fold, suggesting high target specificity. Neither RAP peptide inhibits neuronal rod formation induced by excitotoxic glutamate, but both inhibit rods induced in human neurons by several PrPC/NOX pathway activators (Aβ, HIV-gp120 protein, and IL-6). Significantly, RAP-103 completely protects against Aβ-induced loss of mature and developing synapses and, at 0.1 nM, reverses rods in both rodent and human neurons (T½ ~ 3 h) even in the continuous presence of Aβ. Thus, this orally available, brain-permeable peptide should be highly effective in reducing rod pathology in multifactorial neurological diseases with mixed proteinopathies acting through PrPC/NOX. [ABSTRACT FROM AUTHOR]

Considerable amounts of fish processing by-products are discarded each year. By developing enzyme technologies for protein recovery and modification, the production of a broad spectrum of food ingredients and industrial products may be possible. Collagen peptides are good food products obtained from fish by-products. Collagen peptides are small pieces of animal collagen, which are beneficial for new cell growth, repairing dead skin cell, blood clots and bone formation. The physicochemical properties of fish collagen peptides are also very important. However, there are very less studies that focus on physicochemical properties of fish collagen peptides so far. This paper describes various functional properties of collagen such as solubility, water-absorption capacity, emulsifying properties, foaming properties and fat-absorption capacity along with amino acid composition and mineral analysis. [ABSTRACT FROM AUTHOR]

Anticancer peptides (ACPs) are short protein sequences; they perform functions like some hormones and enzymes inside the body. The role of any protein or peptide is related to its structure and the sequence of amino acids that make up it. There are 20 types of amino acids in humans, and each of them has a particular characteristic according to its chemical structure. Current machine and deep learning models have been used to classify ACPs problems. However, these models have neglected Amino Acid Repeats (AARs) that play an essential role in the function and structure of peptides. Therefore, in this paper, ACPs offer a promising route for novel anticancer peptides by extracting AARs based on N-Grams and k-mers using two peptides' datasets. These datasets pointed to breast and lung cancer cells assembled and curated manually from the Cancer Peptide and Protein Database (CancerPPD). Every dataset consists of a sequence of peptides and their synthesis and anticancer activity on breast and lung cancer cell lines. Five different feature selection methods were used in this paper to improve classification performance and reduce the experimental costs. After that, ACPs were classified using four classifiers, namely AdaBoost, Random Forest Tree (RFT), Multi-class Support Vector Machine (SVM), and Multi-Layer Perceptron (MLP). These classifiers were evaluated by applying five well-known evaluation metrics. Experimental results showed that the breast and lung ACPs classification process provided an accurate performance that reached 89.25% and 92.56%, respectively. In terms of AUC, it reached 95.35% and 96.92% for both breast and lung ACPs, respectively. The proposed classifiers performed competently somewhat equally in AUC, accuracy, precision, F-measures, and recall, except for Multi-class SVM-based feature selection, which showed superior performance. As a result, this paper significantly improved the predictive performance that can effectively distinguish ACPs as virtual inactive, experimental inactive, moderately active, and very active. [ABSTRACT FROM AUTHOR]

The assembly of the β-amyloid peptide (Aβ) to form oligomers and fibrils is closely associated with the pathogenesis and progression of Alzheimer's disease. Aβ is a shape-shifting peptide capable of adopting many conformations and folds within the multitude of oligomers and fibrils the peptide forms. These properties have precluded detailed structural elucidation and biological characterization of homogeneous, well-defined Aβ oligomers. In this paper, we compare the structural, biophysical, and biological characteristics of two different covalently stabilized isomorphic trimers derived from the central and C-terminal regions Aβ. X-ray crystallography reveals the structures of the trimers and shows that each trimer forms a ball-shaped dodecamer. Solution-phase and cell-based studies demonstrate that the two trimers exhibit markedly different assembly and biological properties. One trimer forms small soluble oligomers that enter cells through endocytosis and activate capase-3/7-mediated apoptosis, while the other trimer forms large insoluble aggregates that accumulate on the outer plasma membrane and elicit cellular toxicity through an apoptosis-independent mechanism. The two trimers also exhibit different effects on the aggregation, toxicity, and cellular interaction of full-length Aβ, with one trimer showing a greater propensity to interact with Aβ than the other. The studies described in this paper indicate that the two trimers share structural, biophysical, and biological characteristics with oligomers of full-length Aβ. The varying structural, assembly, and biological characteristics of the two trimers provide a working model for how different Aβ trimers can assemble and lead to different biological effects, which may help shed light on the differences among Aβ oligomers. [ABSTRACT FROM AUTHOR]

Human infection with the intestinal nematode Strongyloides stercoralis is persistent unless effectively treated, and potentially fatal in immunosuppressed individuals. Epidemiological data are lacking, partially due to inadequate diagnosis. A rapid antigen detection test is a priority for population surveillance, validating cure after treatment, and for screening prior to immunosuppression. We used a targeted analysis of open access 'omics' data sets and used online predictors to identify S. stercoralis proteins that are predicted to be present in infected stool, Strongyloides-specific, and antigenic. Transcriptomic data from gut and non-gut dwelling life cycle stages of S. stercoralis revealed 328 proteins that are differentially expressed. Strongyloides ratti proteomic data for excreted and secreted (E/S) proteins were matched to S. stercoralis, giving 1,057 orthologues. Five parasitism-associated protein families (SCP/TAPS, prolyl oligopeptidase, transthyretin-like, aspartic peptidase, acetylcholinesterase) were compared phylogenetically between S. stercoralis and outgroups, and proteins with least homology to the outgroups were selected. Proteins that overlapped between the transcriptomic and proteomic datasets were analysed by multiple sequence alignment, epitope prediction and 3D structure modelling to reveal S. stercoralis candidate peptide/protein coproantigens. We describe 22 candidates from seven genes, across all five protein families for further investigation as potential S. stercoralis diagnostic coproantigens, identified using open access data and freely-available protein analysis tools. This powerful approach can be applied to many parasitic infections with 'omic' data to accelerate development of specific diagnostic assays for laboratory or point-of-care field application. Author summary: The worm Strongyloides stercoralis causes infectious disease in people throughout tropical and sub-tropical regions, leading to an extensive reduction in quality of life and even death. Millions of people are at risk of infection with this parasite and improved diagnostic and control methods and technologies are urgently required. Currently, most diagnosis is carried out through methods involving visual inspection of patient's faeces, which has a number of drawbacks, particularly its poor sensitivity. This paper presents a new method to develop improved diagnostic tests for S. stercoralis, by computational analysis of publicly available gene and protein sequences to predict proteins that may be detectable in faeces. This would enable the development of rapid diagnostic tests in the form of lateral flows or dipsticks, with better predictive ability and fewer drawbacks than current diagnostic methods. A number of potential proteins, predicted to have all the desired characteristics for use in such tests were found through the new method and have been presented in this paper. With validation, new diagnostic tests for S. stercoralis could be developed from these results and the computational approach could be used to target other parasitic diseases. [ABSTRACT FROM AUTHOR]

In many terrestrial ecosystems, the Apis mellifera species played an essential role, being one of the most beneficial insects worldwide. Bee venom (BV) has the role of protecting the bee colony from predators. Among the pharmacological activities of BV are: antibacterial, anti-inflammatory, anticancer, antimutagenic, radioprotective and even antiviral activity. The manifestation of the therapeutic potential is due to the bioactive compounds of BV, the main ones being melittin, phospholipase A2 and apamin, but hyaluronidase, mast cell degranulation peptide and secapin are also relevant for bioactivity. The purpose of this paper is to highlight the biotechnological potential, but also the applicability in the medical field as alternative methods to the use of antibiotics. [ABSTRACT FROM AUTHOR]

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PK34 is a D29 mycobacteriophage-derived anti-microbial peptide (AMP) with anti-Mycobacterium tuberculosis activity. It is expected to become an auxiliary drug for the treatment of M. tuberculosis infection, or as a template for the development of anti-M. tuberculosis drugs. The focus of this paper is to obtain recombinant PK34 by a novel method of prokaryotic expression and purification by affinity chromatography. The minimum inhibitory concentration (MIC) of recombinant PK34 was better than that of synthetic PK34 as measured by the microplate-based Alamar Blue assay (MABA). In order to further compare the different anti-bacterial effects of PK34 obtained by the two methods on M. tuberculosis, the bacterial changes after drug incubation were observed at the microscopic level by transmission electron microscopy (TEM). In order to apply PK34 to clinical treatment earlier in the future, this paper tested the maximum non-toxic concentration of recombinant PK34 to the two most studied immune cells, RAW264.7 and THP-1, through cytotoxicity experiments. The maximum non-toxic concentration was the same as the MIC of recombinant PK34 to M. tuberculosis H37Rv, and both were 12.5 μg/mL. The monoclonal antibodies against PK34 and their hybridoma cell lines were prepared using recombinant PK34 as the antigen. Next, we obtained the gene sequence of the monoclonal antibody, which was prepared for the basic research of PK34 in M. tuberculosis treatment. In addition, the possible molecular docking mode between PK34 and trehalose-6,6-dimycolate (TDM) was predicted by AI simulation. To sum up, this paper provides a new idea for the birth of more new AMPs of the same type as PK34 in the future. Key points: • Design and prepare a novel recombinant PK34 anti-microbial peptide. • Recombinant PK34 has higher purity and anti-bacterial activity than synthetic PK34. • The monoclonal antibody against recombinant PK34 was prepared and sequenced. [ABSTRACT FROM AUTHOR]

Peptide identification from tandem mass spectrometry data is a fundamental task in computational proteomics. Traditional algorithms perform well when facing unmodified peptides. However, when peptides have post-translational modifications (PTMs), these methods cannot provide satisfactory results. Recently, open search methods have been proposed to identify peptides with PTMs. While the performance of these new methods is promising, the identification results vary greatly with respect to the quality of tandem mass spectra and the number of PTMs in peptides. This motivates us to systematically study the relationship between the performance of open search methods and the quality parameters of tandem mass spectrometry data as well as the number of PTMs in peptides. In this paper, we have proposed an analytical model derived from simulated data to describe the relationship between the probability of obtaining correct results and the spectrum quality as well as the number of PTMs. The proposed model is verified using 1,464,146 real experimental spectra. The consistent trend observed in both simulated data and real data reveals the necessary conditions to effectively apply open search methods. Source code of our study is available at http://bioinformatics.ust.hk/PST.html. [ABSTRACT FROM AUTHOR]

Polymer models are a widely used tool to study the prebiotic formation of metabolism at the origins of life. Counts of the number of reactions in these models are often crucial in probabilistic arguments concerning the emergence of autocatalytic networks. In the first part of this paper, we provide the first exact description of the number of reactions under widely applied model assumptions. Conclusions from earlier studies rely on either approximations or asymptotic counting, and we show that the exact counts lead to similar, though not always identical, asymptotic results. In the second part of the paper, we investigate a novel model assumption whereby polymers are invariant under spatial rotation. We outline the biochemical relevance of this condition and again give exact enumerative and asymptotic formulae for the number of reactions. [ABSTRACT FROM AUTHOR]

The purpose of the paper was to explore the effect of adding different levels of soybean active peptides to the diet on the growth performance, carcass traits, serum biochemical indexes and intestinal microorganisms of finishing pigs. A total of 120 finishing pigs with a weight of (72.40±1.10) kg were randomly divided into four groups, with three replicates in each group and 10 pigs in each replicate. The finishing pigs in the control group were fed a basic diet, and group A, group B and group C added 0.2%, 0.4% and 0.6% soybean active peptides in the basic diet, respectively. The experiment lasted for 42 days. The results showed that the average daily gain of the finishing pigs was significantly increased by adding soybean active peptide (P<0.05). Compared with the control group, the feed-to-weight ratio of the group B was significantly reduced (P<0.05), and the feed-to-weight ratio and average back fat thickness of the group C were significantly reduced ( P<0.05). Adding soybean active peptide could improve the meat color and significantly reduce the dripping loss of the finishing pigs in the group B and group C (P<0.05). Compared with the control group, the content of serum MDA in the experimental groups decreased significantly (P<0.05), the content of serum BUN in the group B and group C decreased significantly (P<0.05), the content of IgM and T-AOC increased significantly (P<0.05). The activity of serum AST and GSH-Px in the group C decreased significantly, and the content of IgG increased significantly (P<0.05). The flora with a relative abundance of more than 1% at the phylum level in each experimental group included Firmicutes, Proteobacterium and Bacteroides, and the relative abundance of Proteobacterium in the group C was significantly lower than that in the control group (P<0.05). The flora with a relative abundance over 1% at the genus level included Actinomycetes, Coprococcus, Clostridium and Enterobacter, and there was no significant difference in the relative abundance of each genus compared with the control group (P>0.05). The study indicates that adding 0.4%~0.6% soybean active peptide to the diet can improve the growth performance, modify carcass traits, adjust serum biochemical indexes, and affect the intestinal microbial composition of finishing pigs. [ABSTRACT FROM AUTHOR]

Vigna bean and common bean have received much attention from the functional food and nutraceutical aspects. Upon hydrolysis of beans protein, bioactive peptides from various conditions are produced, with health-promoting properties and a broad spectrum of biological activities, offering nutraceutical or therapeutic potential. There have been few comprehensive investigations into improving the bioactivity and functionality of peptides from vigna and common beans. Therefore, this article describes the key parameters impacting bean derived peptide bioactivity, as well as approaches to improve it. This paper includes a review of papers indicating the stability of peptides obtained from beans under simulated gastrointestinal digestion conditions, as well as some insights into the mechanisms of action of those peptides and their relationship with structure. This review outlines important criteria for rationally designing and selecting bean bioactive peptides with intact structure and therapeutic potential in vivo. This study could be beneficial when conducting future investigations on vigna and common bean protein hydrolysates in vitro or in vivo and the knowledge gained could help with the incorporation of these new bean peptides into functional foods. [ABSTRACT FROM AUTHOR]

CD47/SIRPα pathway is a new breakthrough in the field of tumor immunity after PD-1/PD-L1. While current monoclonal antibody therapies targeting CD47/SIRPα have demonstrated some anti-tumor effectiveness, there are several inherent limitations associated with these formulations. In the paper, we developed a predictive model that combines next-generation phage display (NGPD) and traditional machine learning methods to distinguish CD47 binding peptides. First, we utilized NGPD biopanning technology to screen CD47 binding peptides. Second, ten traditional machine learning methods based on multiple peptide descriptors and three deep learning methods were used to build computational models for identifying CD47 binding peptides. Finally, we proposed an integrated model based on support vector machine. During the five-fold cross-validation, the integrated predictor demonstrated specificity, accuracy, and sensitivity of 0.755, 0.764, and 0.772, respectively. Furthermore, an online bioinformatics tool called CD47Binder has been developed for the integrated predictor. This tool is readily accessible on http://i.uestc.edu.cn/CD47Binder/cgi-bin/CD47Binder.pl. [ABSTRACT FROM AUTHOR]

Ongoing research is gradually broadening the idea of cancer treatment, with attention being focused on nanoparticles to improve the stability, therapeutic efficacy, targeting, and other important metrics of conventional drugs and traditional drug delivery methods. Studies have demonstrated that drug delivery carriers based on biomaterials (e.g., protein nanoparticles and lipids) and inorganic materials (e.g., metal nanoparticles) have potential anticancer effects. Among these carriers, self-assembled proteins and peptides, which are highly biocompatible and easy to standardize and produce, are strong candidates for the preparation of anticancer drugs. Breast cancer (BC) and cervical cancer (CC) are two of the most common and deadly cancers in women. These cancers not only threaten lives globally but also put a heavy burden on the healthcare system. Despite advances in medical care, the incidence of these two cancers, particularly CC, which is almost entirely preventable, continues to rise, and the mortality rate remains steady. Therefore, there is still a need for in-depth research on these two cancers to develop more targeted, efficacious, and safe therapies. This paper reviews the types of self-assembling proteins and peptides (e.g., ferritin, albumin, and virus-like particles) and natural products (e.g., soy and paclitaxel) commonly used in the treatment of BC and CC and describes the types of drugs that can be delivered using self-assembling proteins and peptides as carriers (e.g., siRNAs, DNA, plasmids, and mRNAs). The mechanisms (including self-assembly) by which the natural products act on CC and BC are discussed. The mechanism of action of natural products on CC and BC and the mechanism of action of self-assembled proteins and peptides have many similarities (e.g., NF-KB and Wnt). Thus, natural products using self-assembled proteins and peptides as carriers show potential for the treatment of BC and CC. [ABSTRACT FROM AUTHOR]

Cancer is the second leading cause of death globally, but conventional anticancer drugs have side effects, mainly due to their non-specific distribution in the body in both cancerous and healthy cells. To address this relevant issue and improve the efficiency of anticancer drugs, increasing attention is being devoted to hydrogel drug-delivery systems for different kinds of cancer treatment due to their high biocompatibility and stability, low side effects, and ease of modifications. To improve the therapeutic efficiency and provide multi-functionality, different types of nanoparticles (NPs) can be incorporated within the hydrogels to form smart hydrogel nanocomposites, benefiting the advantages of both counterparts and suitable for advanced anticancer applications. Despite many papers on non-peptide hydrogel nanocomposites, there is limited knowledge about peptide-based nanocomposites, specifically in anti-cancer drug delivery. The aim of this short but comprehensive review is, therefore, to focus attention on the synergies resulting from the combination of NPs with peptide-based hydrogels. This review, which includes a survey of recent advances in this kind of material, does not aim to be an exhaustive review of hydrogel technology, but it instead highlights recent noteworthy publications and discusses novel perspectives to provide valuable insights into the promising synergic combination of peptide hydrogels and NPs for the design of novel anticancer drug delivery systems. [ABSTRACT FROM AUTHOR]

Low-molecular-weight peptide gelators are a versatile class of compounds able to form gels under a variety of conditions, even via simple ultrasound sonication. In this paper, the ability of Boc-L-Phe-D-Oxd-L-Phe-OBn to gelate three organic solvents (toluene, tert-butyl methyl ether, and ethanol) was evaluated. The rheological behaviour of the materials was assessed via strain sweep analysis, while the fibrous network was analysed via optical microscopy on the wet gels. The gel obtained from toluene is a highly transparent material, and the one from ethanol appears translucent, while the one from tert-butyl methyl ether is opaque. These gels were used to study the reversible light-induced transformation from spyropiran (SP) to merocyanine (MC) and back, as a model system to check the effect of the gel medium onto the rection kinetic. We observed that the solvent used to form the organogels has a crucial effect on the reaction, as gels from aprotic solvents stabilize the SP form, while the ones from protic solvents stabilize the MC form. We thus obtained a solid support to stabilize the two photochromic species just by changing the solvent polarity. Moreover, we could demonstrate that the self-assembled gels do not interfere with the light-driven conversion process, either starting from SP or MC, thus representing a valid and economical photochromic material. [ABSTRACT FROM AUTHOR]