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We developed a simple, paper‐based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter‐balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes. One end of the paper strip was cut into a sharp point and positioned near the inlet of a MS. The stacked analyte bands move toward the paper tip with the EOF where they are ionized by paper spray. The device was applied to analysis of PFAS in tap water with sub part‐per‐trillion detection limits in less than ten minutes with no sample pretreatment. Analysis of opioids in urine also occurs in minutes. The crucial parameters to enable stacking, separation, and MS ionization of both positively and negatively charged analytes were determined and optimized. Experimental and computational modeling studies confirm the electrokinetic stacking and analyte transport mechanisms. On‐paper separations were carried out by stacking analyte bands at different locations depending on their electrophoretic mobility, achieving baseline separation in some cases. [ABSTRACT FROM AUTHOR]

An unprecedented and direct PS‐MS (paper spray ionization mass spectrometry) method was proposed for the detection of native peptides, that is, glutathiones (GSHs), homoglutathiones (hGSHs), and phytochelatins (PCs), in basil (Ocimum basilicum L.) roots before and after cadmium exposure. The roots were submitted to cold maceration followed by sonication with formic acid as the extractor solvent for sample preparation. PS‐MS was used to analyze such extracts in the positive mode, and the results allowed for the detection of several GSHs, hGSHs, and PCs. Some of these PCs were not distinguished in the control samples, that is, basil roots not exposed to cadmium. Other PCs were noticed in both types of roots, uncontaminated and cadmium‐contaminated, but the intensities were higher in the former samples. Moreover, long‐time exposure to cadmium stimulated the formation of some of these PCs and their cadmium complexes. The results, therefore, provided some crucial insights into the defense mechanism of plants against an external stress condition due to exposure to a toxic heavy metal. The present study represents a promising alternative to investigate other crucial physiological processes in plants submitted to assorted stress conditions. [ABSTRACT FROM AUTHOR]

A simple method is described for the patterned deposition of Teflon on paper to create an integrated platform for parallel organic synthesis and cell-based assays. Solvent-repelling barriers made of Teflon-impregnated paper confine organic solvents to specific zones of the patterned array and allow for 96 parallel flow-through syntheses on paper. The confinement and flow-through mixing significantly improves the peptide yield and simplifies the automation of this synthesis. The synthesis of 100 peptides ranging from 7 to 14 amino acids in length gave over 60 % purity for the majority of the peptides (>95 % yield per coupling/deprotection cycle). The resulting peptide arrays were used in cell-based screening to identify 14 potent bioactive peptides that support the adhesion or proliferation of breast cancer cells in a 3D environment. In the future, this technology could be used for the screening of more complex phenotypic responses, such as cell migration or differentiation. [ABSTRACT FROM AUTHOR]

A single amino acid in a peptide sequence can play an important role to tune the self‐assembly and hydrogelation behaviour. Here, a C‐terminal cysteine‐containing ultrashort peptide hydrogelator forms hydrogel through non‐covalent and covalent interactions. Interestingly, the hydrogel is insoluble in water and buffer solutions at different pH values (1‐13) and is thixotropic and injectable. In recent years, removing dyes from contaminated water has become a significant concern because of the shortage of freshwater resources. Therefore, the adsorption of dyes through a reliable, straightforward, nontoxic, cheap, and environmentally friendly adsorbent has become a popular topic. Hence, the hydrogelator was exploited to remove organic dyes from wastewater, harnessing its applicability in the gel phase and solid supports (filter paper and cotton). [ABSTRACT FROM AUTHOR]

The measurement of proglucagon-derived peptides (PGDPs) is a challenging task mainly due to major overlaps in their molecular sequence in addition to their low circulating levels. Here, we present the technical characteristics of novel ELISA assays measuring C-peptide and all six PGDPs including, for the first time, major proglucagon fragment (MPGF), and we validate them by performing a pilot in vivo cross-over randomized clinical trial on whether coffee consumption may affect levels of circulating PGDPs. The performance and technical characteristics of novel ELISA assays from Ansh measuring GLP-1, GLP-2, oxyntomodulin, glicentin, glucagon, MPGF and C-peptide were first evaluated in vitro in procured samples from a commercial vendor as well as in deidentified human samples from three previously performed clinical studies. Their performance was further evaluated in vivo in the context of a cross-over randomized controlled trial, in which 33 subjects consumed in random order and together with a standardized meal, 200 ml of either (a) instant coffee with 3 mg/kg caffeine, or (b) instant coffee with 6 mg/kg caffeine, (c) or water. All assays demonstrated high accuracy (spike and recovery and average linearity recovery ±15%), precision (inter-assay CV ≤ 6.4%), specificity (no significant cross-reactivities) and they were sensitive in low concentrations. Measurements of glicentin in archived random human samples using the Ansh assay correlated strongly with the glicentin measurements of Mercodia assay (r = 0.968) and of GLP-1 modestly with Millipore GLP-1 assay (r = 0.440). Oxyntomodulin, glicentin and glucagon concentrations were 2–5 fold higher in plasma compared to serum and serum concentrations correlated modestly (for oxyntomodulin and glicentin) or poorly (for glucagon) with the plasma concentrations. The evaluated assays detected a postprandial increase of gut-secreted PGDPs (GLP-1, GLP-2, oxyntomodulin and glicentin) and a postprandial decrease of pancreas-secreted PGDPs (glucagon, MPGF) in response to consuming coffee in comparison to consuming water with breakfast (enter here composition of breakfast). Only coffee consumption at the high dose alter levels of gut-secreted PGDPs and both at low and high dose to lower levels of pancreas-secreted PGDPs compared to water consumption during breakfast. Accurate, precise and specific measurement of six PGDPs is possible with novel assays. A randomized controlled trial demonstrated in vivo utility of those assays and supports the notion that coffee may exert part of its beneficial effects on glucose homeostasis in the short term through the regulation of PGDPs. • Sequences of PGDPs are overlapping and their low circulating levels make their measurement difficult. • Novel assays can perform an accurate, precise, and specific measurement of PGDPs. • Regulation of glucose homeostasis by coffee may occur through altering circulating levels of PGDPs. [ABSTRACT FROM AUTHOR]

Drug–drug interaction (DDI) assessments are well defined in health authority guidelines for small molecule drugs, and US Food and Drug Administration (FDA) draft guidance is now available for therapeutic proteins. However, there are currently no regulatory guidelines outlining DDI assessments for therapeutic peptides, which poses significant uncertainty and challenges during drug development for this heterogenous class of molecules. A cross‐industry peptide DDI working group consisting of experts from 10 leading companies was formed under the sponsorship of the European Federation of Pharmaceutical Industries and Associations. We aimed to capture the range of DDI studies undertaken for peptide drugs by (i) anonymously surveying relevant companies involved in peptide drug development to better understand DDI study type/timing currently performed and (ii) compiling a database containing in vitro / clinical DDI data from submission packages for recently approved peptide drugs. Our analyses highlight significant gaps and uncertainty in the field. For example, the reported timing of in vitro peptide DDI studies, if performed, vary substantially across responding companies from early research to phase III. Nearly all in vitro cytochrome P450 / transporter inhibition studies reported in the survey were negative. For the few positive hits reported, no clinical follow‐up studies were performed, questioning the clinical relevance of these findings. Furthermore, available submission packages reveal DDI likelihood is low for peptides >2 kDa, making it reasonable to adopt a risk‐based approach during drug development for larger peptides. By benchmarking the landscape of peptide DDI activities across the industry, we set the stage for future discussions with health authorities on harmonizing peptide DDI approaches. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel dual-functional probe FAHK was design and synthesized based on copper peptide backbone. • FAHK showed sequential response towards Cu2+/Hg2+ and S2− via fluorescent and colorimetric methods. • The detection limit of 37.1 nM for Cu2+, 20.8 nM for Hg2+ and 0.27 μM/0.12 μM for S2−, respectively. • FAHK has low toxicity and was successfully used to image Cu2+, Hg2+ and S2− in living cells. • Test strips of FAHK were prepared for rapid and visual detection for Cu2+, Hg2+ and S2− with naked eye. In this study, a novel peptide-based fluorescent and colorimetric dual-functional probe (FAHK) was designed and synthesized by simulating the structure of copper peptide. FAHK exhibited high selectivity and rapid response to Cu2+ and Hg2+ with two non-fluorescence ensembles FAHK- Cu2+ and FAHK- Hg2+ formation by the 2:1 coordination mode, and the limits of detection for Cu2+ and Hg2+ were 37.1 nM and 20.8 nM, respectively. FAHK showed a naked eye colorimetric response for Cu2+ and Hg2+ in an aqueous solutions under visible light. As two new promising cascade probes, FAHK- Cu2+ and FAHK- Hg2+ ensemble were used for sequential selective recognition of S2− according to the displacement approach with fluorescence "turn-on" response and colorimetric change, and the limit of detection were 0.27 μM (FAHK -Cu2+ ensemble) and 0.12 μM (FAHK -Hg2+ ensemble) for S2−, which were well below the safety level the H 2 S standard in drinking waters (14.8 µM, WHO guidelines). What' more, in view of low toxicity and biocompatibility, the potential application of FAHK in biological systems was demonstrated via living cells imaging. More importantly, FAHK could also be made into the paper test strips for visual detection of Cu2+, Hg2+ and S2− with the naked eye under 365 nm UV light and visible light, which suggested that better portability and operation simplicity that is favourable for on-site analysis. [ABSTRACT FROM AUTHOR]

Phage display biopanning is used to identify peptides that show material-selective adsorption, effectively distinguishing between the cellulose of paper and the printed toner of standard office laser printers. These genetically selected 12mer peptides can selectively coat either non-printed cellulose or printed toner patterns. Furthermore, triazolindione ligation chemistry is exploited to introduce, for example, dyes or functional peptides selectively to the coatings. The strategy offers an easy access towards the patterned functionalization of paper-based materials, which potentially is of relevance for low-cost diagnostics or biomedical devices. [ABSTRACT FROM AUTHOR]

The atomistic description of the folding process of a structureless chain of amino acids to a functioning protein is still considered to be a challenge for computational biophysics. An in-depth understanding of protein-folding can be achieved through atomistic dynamics accounting for the solvent effects, combined with the theoretical description of conformational changes in shorter polypeptide chains. The present paper studies the folding transitions in short polypeptide chains consisting of 11 alanine residues in explicit solvent employing all-atom molecular dynamics. The multiple observed folding ↔ unfolding events of the peptide are interpreted as a dynamic process and rationalised through the analysis of the potential energy surface of the system. It is demonstrated that alanine polypeptide folding dynamics is governed by the backbone dihedral angles and involves the formation of spontaneously folded α -helices which emerge and live for ca. 1–20 picoseconds. The helical content within the polypeptide at different temperatures was quantified through a statistical mechanics approach, which showed a reasonable agreement with the results of molecular dynamics simulations and experiments performed for alanine-rich peptides. [ABSTRACT FROM AUTHOR]

In vitro bioefficacies of the different antimicrobial peptides (AMPs) were tested against three bacteria using paper disc and micro-dilution broth method. Nine different cationic AMPs viz. D4E1, PEP11, ESF1, ESF4, ESF5, ESF6, ESF12, ESF13 and ESF17 exhibiting variable amino acid compositions and charges, were used for the present investigation. Among the various AMPs tested against Xanthomonas axonopodis pv. punicae (Xap), Xanthomonas axonopodis pv. citri (Xac) and Xanthomonas axonopodis pv. malvacearum (Xam), the peptide D4E1 (net charge + 8) was the most effective AMP against all the three Xanthomonas sp. followed by PEP11, ESF12 and ESF1 having net charge +4. The peptide ESF13 was not effective against all the three bacteria while ESF4 was not effective against Xap and Xac whereas ESF6 was also not effective against Xac. AntiMicrobial peptides when tested in vitro through micro-dilution broth method showed that the inhibition growth per cent against Xap was greater than 90% (MIC90) for D4E1, PEP11, ESF17, ESF5 and ESF12. For Xac, D4E1, PEP11, ESF17, ESF5, ESF6, ESF1 and ESF12 showed the inhibition growth percent greater than 90% (MIC90). For Xam, the inhibition growth per cent was seen greater than 90% (MIC90) for D4E1, PEP11, ESF17, ESF1 and ESF12. The most promising peptide D4E1 exhibited better stability against endogenous proteases which recorded only 10.08 % hemolysis at a very high i.e.100 μM concentration. The D4E1 peptides appears to be a promising candidate to be explanted through gene manipulation to control bacterial blight of pomegranate. [ABSTRACT FROM AUTHOR]

Bacillus anthracis is a fatal biological warfare agent, with a mortality rate of almost 100% when the bacteria are inhaled. Therefore, developing a biosensor for rapidly detecting B. anthracis spores in the ambient air is critical. Conventional techniques tend to be time-consuming, labor-intensive, and require highly trained personnel, thereby preventing rapid onsite detection. Moreover, low-cost, stable probes are required for continuous monitoring of multiple airborne targets. This study presents a paper-based electrochemical peptide sensor for rapid, label-free, sensitive, and economical quantification of liquid-borne and airborne Bacillus subtilis spores, widely used nonpathogenic B. anthracis simulant spores. These sensors were fabricated using wax printing on Whatman filter paper along with stencil-printed carbon paste electrodes and Ag/AgCl ink, as well as subsequent peptide (NHFLPKV) immobilization. These low-cost quickly fabricated sensors were characterized by differential pulse voltammetry and could detect spore concentrations as low as 6.9 × 102 colony-forming units (CFU) mL-1 in 30 min with high specificity towards the spores and stability. Furthermore, spore concentrations were determined from air samples obtained using the BioSampler, which demonstrated that these measurements agreed with those using the plate-counting assay; therefore, the surface proteins of the spores were intact through sampling with the BioSampler. These paper-based peptide sensors can be used for onsite rapid and continuous airborne spore-monitoring systems. • The first study to use a peptide-immobilized electrochemical paper-based sensor for detection of whole bacteria. • Rapid, label-free, sensitive, and economical quantification of airborne B. subtilis spores is presented. • The sensors detected spore concentrations as low as 6.9 × 102 CFU/mL in 30 min with low-cost and fast fabrication. • Measurements of air-sampled spores agreed with those using the plate-counting assay. • The surface proteins of the spores were intact through sampling with the BioSampler. [ABSTRACT FROM AUTHOR]

Required metrological tools, such as higher order reference measurements procedures, pure substance and matrix certified reference materials, are established for small well defined molecules. Difficulties still remain in the provision of SI traceable standards in the area of larger biomolecules such as peptides/proteins. The provision of Primary Calibration Reference Services has been identified as a core technical competency for National Measurement Institutes (NMIs). A concept has been elaborated by the Focus Group I on peptide/protein purity for the strategic planning of ongoing Key Comparisons of the Protein Analysis Working Group (PAWG) within the Comité Consultatif pour la Quantité de Matière (CCQM). The assignment of the mass fraction content of high purity peptide/protein materials will be the subject of the CCQM-K115/P55.2 comparison series to directly support NMI services and certified reference materials currently being provided by NMIs. [ABSTRACT FROM AUTHOR]

Abstract: We report that hydrophilic oxidized multiwalled carbon nanotube papers (CNPs) were efficient substrates for attachment, spreading, and proliferation of MG-63 cells. Complete spreading occurred in the first 4h of culture even without complete serum or pre-adsorbed adhesion proteins such as collagen or fibronectin. By contrast, the density of adherent cell on hydrophobic CNPs was low. Spreading did not happen after 24h of culture in absence of serum proteins and growth factors on such papers. Cell viability concomitantly decreased. We also observed that a short RGD peptide, designed to adsorb on both hydrophobic and hydrophilic CNPs, enhanced adhesion, spreading, and proliferation only on hydrophilic CNPs. By contrast, adsorbed fibronectin triggers cell adhesion and spreading on both types of CNPs. Our results show that the imitation of tissue basal membranes with the nanofibrous structure of CNPs is insufficient to trigger the proliferation and spread of cells. Chemical cues are also needed for cells to spread. CNPs, however, offer a better substrate for adhesion protein absorption than do non-porous polymers. [Copyright &y& Elsevier]

Abstract: Protein ORIGAMI ( http://ibg.kit.edu/protein_origami) is a browser‐based web application that allows the user to create straightforward 3D paper models of folded peptides for research, teaching and presentations. An amino acid sequence can be turned into α‐helices, β‐strands and random coils that can be printed out and folded into properly scaled models, with a color code denoting the biophysical characteristics of each amino acid residue (hydrophobicity, charge, etc.). These models provide an intuitive visual and tactile understanding of peptide interactions with other partners, such as helix‐helix assembly, oligomerization, membrane binding, or pore formation. Helices can also be displayed as a helical wheel or helical mesh in 2D graphics, to be used in publications or presentations. The highly versatile programme Protein ORIGAMI is also suited to create less conventional helices with arbitrary pitch (e.g., 310‐helix, π‐helix, or left‐handed helices). Noncanonical amino acids, labels and different terminal modifications can be defined and displayed at will, and different protonation states can be shown. In addition to the web application, the program source code can be downloaded and installed locally on a PC. The printed paper models can be readily used for daily research and discussions, just as for educational purposes and teaching. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:403–409, 2018. [ABSTRACT FROM AUTHOR]

Emollients are topical agents with moisturizing, lubricating and smoothing properties. The most important action of emollients is restoring the disturbed epidermal barrier. This effect is achieved by various mechanisms: occlusive properties, attraction and keeping the water within the stratum corneum and supplying the physiological lipids and peptides, that lack in the disturbed epidermis. The final effects of emollients are reduction of inflammation, decrease of pruritus and better appearance of the skin. Emollients are the essential part of the therapy of many inflammatory skin diseases with disturbed epidermal barrier. They are used in the treatment of atopic dermatitis, psoriasis, keratinization disorders, chronic eczema, pruritic diseases and many other dermatoses. Emollients are often the adjuvant therapy, which is used together with topical corticosteroids or calcineurin inhibitors. There are several possible types of therapy: continuous, intermittent or proactive. This paper summarizes the knowledge about emollients, their mechanisms of action, the indications and proper way of application. [ABSTRACT FROM AUTHOR]

Two new antibacterial peptides, denominated as Dominulin A and B, have been found on the cuticle and in the venom of females of the social paper wasp Polistes dominulus. The amino acidic sequence of the two peptides, determined by mass spectrometry, is INWKKIAE VGGKIL SSL for Dominulin A (MW = 1854 Da) and INWKKIAEIGKQVL SAL (MW = 1909 Da) for Dominulin B. Their presence on the cuticle was confirmed using MALDI-TOF by means of micro-extractions and direct analyses on body parts. The presence in the venom and the primary structure of the dominulins suggest their classification in the mastoparans, a class of peptides found in the venom of other Aculeate hymenoptera. Their antimicrobial action against Gram+ and Gram− bacteria fits in the range of the best natural antimicrobial peptides. Dominulins can represent an important defense of the colony of Polistes dominulus against microbial pathogens. [Copyright &y& Elsevier]

Six peptide toxins (Magi 1–6) were isolated from the Hexathelidae spider Macrothele gigas. The amino acid sequences of Magi 1, 2, 5 and 6 have low similarities to the amino acid sequences of known spider toxins. The primary structure of Magi 3 is similar to the structure of the palmitoylated peptide named PlTx-II from the North American spider Plectreurys tristis (Plectreuridae). Moreover, the amino acid sequence of Magi 4, which was revealed by cloning of its cDNA, displays similarities to the Na+ channel modifier δ-atracotoxin from the Australian spider Atrax robustus (Hexathelidae). Competitive binding assays using several 125I-labelled peptide toxins clearly demonstrated the specific binding affinity of Magi 1–5 to site 3 of the insect sodium channel and also that of Magi 5 to site 4 of the rat sodium channel. Only Magi 6 did not compete with the scorpion toxin LqhαIT in binding to site 3 despite high toxicity on lepidoptera larvae of 3.1 nmol/g. The Kis of other toxins were between 50 pM for Magi 4 and 1747 nM for Magi 1. In addition, only Magi 5 binds to both site 3 in insects (Ki=267 nM) and site 4 in rat brain synaptosomes (Ki=1.2 nM), whereas it showed no affinities for either mammal binding site 3 or insect binding site 4. Magi 5 is the first spider toxin with binding affinity to site 4 of a mammalian sodium channel. [Copyright &y& Elsevier]

In this paper, we analyse the claim that oxytocin is a 'social neuropeptide'. This claim originated from evidence that oxytocin was instrumental in the initiation of maternal behaviour and it was extended to become the claim that oxytocin has a key role in promoting social interactions between individuals. We begin by considering the structure of the scientific literature on this topic, identifying closely interconnected clusters of papers on particular themes. We then analyse this claim by considering evidence of four types as generated by these clusters: (i) mechanistic studies in animal models, designed to understand the pathways involved in the behavioural effects of centrally administered oxytocin; (ii) evidence from observational studies indicating an association between oxytocin signalling pathways and social behaviour; (iii) evidence from intervention studies, mainly involving intranasal oxytocin administration; and (iv) evidence from translational studies of patients with disorders of social behaviour. We then critically analyse the most highly cited papers in each segment of the evidence; we conclude that, if these represent the best evidence, then the evidence for the claim is weak. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'. [ABSTRACT FROM AUTHOR]

In this paper, a microfluidic paper-based analytical device is presented for sensitively detecting peptides based on the specific recognition of aptamer and the amplification strategy of hybridization chain reaction (HCR). The aptamer/initiation strand (AP/IS) was designed for the specific target recognition, and the presence of the target peptide could release the initiating sequence from the AP/IS. The released IS could trigger the HCR between two hairpin probes, which could complete the detection for the targets indirectly when the electrochemiluminescence (ECL) probe (Ru(phen)32+) is introduced into the double-strand DNA grooves,which could produce a significantly amplified ECL signal output. Mucin-1 was employed as a model peptide, and the detection limit of the proposed assay is calculated as 8.33 pMwith a range from 25 pM to 50 nM. The novel sensing platform can be widened for the detection of other kinds of peptides as well as potentials used for sensitively detecting other biomolecules, and even cells. [ABSTRACT FROM AUTHOR]

Background: Minimotifs are short peptide sequences within one protein, which are recognized by other proteins or molecules. While there are now several minimotif databases, they are incomplete. There are reports of many minimotifs in the primary literature, which have yet to be annotated, while entirely novel minimotifs continue to be published on a weekly basis. Our recently proposed function and sequence syntax for minimotifs enables us to build a general tool that will facilitate structured annotation and management of minimotif data from the biomedical literature. Results: We have built the MimoSA application for minimotif annotation. The application supports management of the Minimotif Miner database, literature tracking, and annotation of new minimotifs. MimoSA enables the visualization, organization, selection and editing functions of minimotifs and their attributes in the MnM database. For the literature components, Mimosa provides paper status tracking and scoring of papers for annotation through a freely available machine learning approach, which is based on word correlation. The paper scoring algorithm is also available as a separate program, TextMine. Form-driven annotation of minimotif attributes enables entry of new minimotifs into the MnM database. Several supporting features increase the efficiency of annotation. The layered architecture of MimoSA allows for extensibility by separating the functions of paper scoring, minimotif visualization, and database management. MimoSA is readily adaptable to other annotation efforts that manually curate literature into a MySQL database. Conclusions: MimoSA is an extensible application that facilitates minimotif annotation and integrates with the Minimotif Miner database. We have built MimoSA as an application that integrates dynamic abstract scoring with a high performance relational model of minimotif syntax. MimoSA's TextMine, an efficient paper-scoring algorithm, can be used to dynamically rank papers with respect to context. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)-6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL-2 family proteins (BCL-2, BCL-XL, BAX and MCL-1) were also investigated. In addition, the RPMI 8226 cell line (IL-6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time- and dose-dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 μmol/l). BCL-2, BCL-XL and MCL-1 showed decreased expression in depsipeptide-treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM. [ABSTRACT FROM AUTHOR]

Chromogranin B (CgB) is a member of the granin family of neuroendocrine secretory proteins, which has been proposed to play a role in secretory granule biogenesis and as a precursor to bioactive peptides. The cloning of CgB in a phylogenetically distant vertebrate, the frog Rana ridibunda, reveals a modest overall homology (35–40%) with mammalian CgB. However, the sequences of the N- and C-terminal regions are more highly conserved (57–65% amino acid identity) and may give rise to novel regulatory peptides. In frog, intense expression of CgB mRNA was observed in particular structures of the brain and in the distal lobe of the pituitary. [Copyright &y& Elsevier]

Cardiovascular Diseases (CVDs) pose a significant global health threat, with rising mortality rates attributed to factors like diabetes, obesity, and an aging population. This paper explores the evolving landscape of micro and nanoscale Drug Delivery Systems (DDSs) to enhance cardiovascular treatment efficacy. Various nanoagents, both organic (e.g., liposomes, dendrimers, polymeric nanoparticles) and inorganic (e.g., carbon nanotubes, silver nanoparticles, iron oxide nanoparticles), are classified and examined. The advantages, limitations, and preparation techniques of nanoagents are discussed, emphasizing their potential in targeted delivery, multifunctionality, minimal side effects, and enhanced efficiency. The anatomical details of the heart, layers of heart walls, and heart functions are presented for contextual understanding. The application of nanoagents in treating specific cardiovascular conditions, such as atherosclerosis, hypertension, myocardial infarction, and coronary artery disease, is thoroughly explored. Evaluation methods for nanoagents, including size and morphology analysis, surface charge determination, and molecular weight evaluation, are outlined. This paper concludes by emphasizing the promising role of nano-drug delivery systems in addressing CVD challenges, urging collaborative efforts for successful translational medicine implementation. Future research directions are proposed, highlighting the potential of peptides, antibodies, and selective nanodelivery systems in advancing cardiovascular care. Challenges like pharmaceutical scale-up, regulatory requirements, and patient preparation are acknowledged, underscoring the need for interdisciplinary collaboration to propel nanocardio medicine into clinical practice. [ABSTRACT FROM AUTHOR]

Electronic noses (e-nose) and optical noses (o-nose) are two emerging approaches for the development of artificial olfactory systems for flavor and smell evaluation. The current work leverages the unique optical properties of semiconducting single-wall carbon nanotubes (SWCNTs) to develop a prototype of a novel paper-based near-infrared optical nose (NIRON). We have drop-dried an array of SWCNTs encapsulated with a wide variety of peptides on a paper substrate and continuously imaged the emitted SWCNTs fluorescence using a CMOS camera. Odors and different volatile molecules were passed above the array in a flow chamber, resulting in unique modulation patterns of the SWCNT photoluminescence (PL). Quartz crystal microbalance (QCM) measurements performed in parallel confirmed the direct binding between the vapor molecules and the peptide-SWCNTs. PL levels measured before and during exposure demonstrate distinct responses to the four tested alcoholic vapors (ethanol, methanol, propanol, and isopropanol). In addition, machine learning tools directly applied to the fluorescence images allow us to distinguish between the aromas of red wine, beer, and vodka. Further, we show that the developed sensor can detect limonene, undecanal, and geraniol vapors, and differentiate between their smells utilizing the PL response pattern. This novel paper-based optical biosensor provides data in real-time, and is recoverable and suitable for working at room temperature and in a wide range of humidity levels. This platform opens new avenues for real-time sensing of volatile chemical compounds, odors, and flavors. • An optical nose based on an array of drop-dried peptide encapsulated SWCNTs was developed. • The biosensor was able to discriminate between various volatile molecules. • The developed sensor is fully recoverable and stable for hours of continuous work. [ABSTRACT FROM AUTHOR]

The diagnosis of Alzheimer's disease (AD) is frequently missed or delayed in clinical practice. To remedy this situation, we developed a screening, paper-based (P-ELISA) platform to detect β-amyloid peptide 1–42 (Aβ42) and provide rapid results using a small volume, easily accessible plasma sample instead of cerebrospinal fluid. The protocol outlined herein only requires 3 μL of sample per well and a short operating time (i.e., only 90 min). The detection limit of Aβ42 is 63.04 pg/mL in a buffer system. This P-ELISA-based approach can be used for early, preclinical stage AD screening, including screening for amnestic mild cognitive impairment (MCI) due to AD. It may also be used for treatment and stage monitoring purposes. The implementation of this approach may provide tremendous impact for an afflicted population and may well prompt additional and expanded efforts in both academic and commercial communities. [ABSTRACT FROM AUTHOR]

A commentary of the paper 'Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology' that appeared recently in Aging Cell. The possible association of a mitochondrial haplogroup with a disease is frequently discussed. The Humanin peptide encoded by the mtDNA has been shown to play an important regulatory role in cell metabolism. There are variants of Humanin caused by different mutations and it is known that the potent form of Humanin, termed S14G, is found naturally in the people of haplogroup U6a7a1a because they have the mutation m.A2672G; however it has not been shown that having this mutation is indeed beneficial. In their paper, the authors suggest that the mitochondrial DNA mutation, m.C2639T, may be beneficial in people who are in haplogroup N1b and also carry APOE4. The mutation changes the common form of Humanin to Humanin P3S. In the study, the researchers looked at a group of Ashkenazi women who were over the age of 95, and found that a higher proportion of them carried APOE4, suggesting that Humanin P3S protected them against the adverse effects of APOE4. A study in a mouse model supported this finding by showing treatment with Humanin P3S reduced APOE4‐induced brain pathology. In the world population, there are about 500,000 Ashkenazi in haplogroup N1b, predominantly in the subgroup N1b1b1; and there are about 9.5 million non‐Ashkenazi people with the mutation m.C2639T and are therefore also in haplogroup N1b and have Humanin P3S. However, the researchers have yet to show Humanin P3S is of benefit in non‐Ashkenazi people. This paper raises the possibility of a therapeutic use of Humanin P3S in the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

White birch (Betula papyrifera) is a dominant tree species of the Boreal Forest. Recent studies have shown that it is fairly resistant to heavy metal contamination, specifically to nickel. Knowledge of regulation of genes associated with metal resistance in higher plants is very sketchy. Availability and annotation of the dwarf birch (B. nana) enables the use of high throughout sequencing approaches to understanding responses to environmental challenges in other Betula species such as B. papyrifera. The main objectives of this study are to 1) develop and characterize the B. papyrifera transcriptome, 2) assess gene expression dynamics of B. papyrifera in response to nickel stress, and 3) describe gene function based on ontology. Nickel resistant and susceptible genotypes were selected and used for transcriptome analysis. A total of 208,058 trinity genes were identified and were assembled to 275,545 total trinity transcripts. The transcripts were mapped to protein sequences and based on best match; we annotated the B. papyrifera genes and assigned gene ontology. In total, 215,700 transcripts were annotated and were compared to the published B. nana genome. Overall, a genomic match for 61% transcripts with the reference genome was found. Expression profiles were generated and 62,587 genes were found to be significantly differentially expressed among the nickel resistant, susceptible, and untreated libraries. The main nickel resistance mechanism in B. papyrifera is a downregulation of genes associated with translation (in ribosome), binding, and transporter activities. Five candidate genes associated to nickel resistance were identified. They include Glutathione S–transferase, thioredoxin family protein, putative transmembrane protein and two Nramp transporters. These genes could be useful for genetic engineering of birch trees. [ABSTRACT FROM AUTHOR]

By establishing both a highly efficient phosphonamidate formation and a RuCp-catalyzed cleavage of an allyl linker, the solid-phase synthesis of Fmoc-(GlyP(OBn))6-OH/DIEA, a protected form of a new type of unnatural peptide α-amino phosphonic acid oligomer (APO), has been realized. [ABSTRACT FROM AUTHOR]

The article discusses the use of diagnostic biomarkers for prediction of adverse early pregnancy outcomes. Topics mentioned include the use of a biomarker for reduction of clinical burden of pregnancy of unknown location cases, the controversies surrounding the use of biomarkers, such as human chorionic gonadotrophin and progesterone, and the categorization of biomarkers in early pregnancy based on their biological origin.

Background: Many groups have been using immunomagnetic reduction (IMR) for assaying plasma amyloid-β 1-40 (Aβ1-40) peptide, Aβ1-42 peptide and total tau protein (T-Tau) in cognitively normal controls (NC), patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD). Tremendous results have been independently reported. Objective: We used traditional knowledge databases (e.g., PubMed, Embase), papers published at international conferences, and private communications to obtain data involving the use of IMR assay for plasma biomarkers of plasma Aβ1-40, Aβ1-42, and T-Tau in NC, aMCI, and ADD. Methods: Results of thirty studies were analyzed, including twenty-five studies published in papers, two studies presented at conferences and three unpublished studies. Results: Among the thirty studies, there were 1189 subjects of NC, 544 aMCI patients and 853 ADD patients. The average value of plasma Aβ1-40 in subjects significantly decreased from NC (59.72 pg/ml) to aMCI (45.92 pg/ml, p < 0.0001), which was no significant different from ADD (48.34 pg/ml, p > 0.05). The average level of plasma Aβ1-42 significantly increased from NC (15.72 pg/ml) to aMCI (17.66 pg/ml, p < 0.0001), which was not significantly different from ADD (19.39 pg/ml, p > 0.05). However, the average level of plasma T-Tau significantly increased from NC (17.92 pg/ml) to aMCI (28.26 pg/ml, p < 0.0001), further significantly increased to AD (35.51 pg/ml, p < 0.001). Conclusions: Plasma Aβ1-40, Aβ1-42, and T-Tau levels are able to discriminate NC from patients with aMCI and ADD. Plasma T-Tau levels are disease-severity dependent. [ABSTRACT FROM AUTHOR]

Background. Colorectal cancer (CRC) is one of the most common cancers in the world, identification of biomarkers for early detection of CRC represents a relevant target. The present study aims to determine serum peptidome patterns for CRC diagnosis. Methods. The present work focused on serum proteomic analysis of 32 health volunteers and 38 CRC by ClinProt Kit combined with mass spectrometry. This approach allowed the construction of a peptide patterns able to differentiate the studied populations. An independent group of serum (including 33 health volunteers, 34 CRC, 16 colorectal adenoma, 36 esophageal carcinoma, and 31 gastric carcinoma samples) was used to verify the diagnostic and differential diagnostic capability of the peptidome patterns blindly. An immunoassaymethod was used to determine serumCEA of CRC and controls. Results. A quick classifier algorithm was used to construct the peptidome patterns for identification of CRC from controls. Two of the identified peaks at m/z 741 and 7772 were used to construct peptidome patterns, achieving an accuracy close to 100% (>CEA, P < 0.05). Furthermore, the peptidome patterns could differentiate validation group with high accuracy. Conclusions. These results suggest that the ClinProt Kit combined with mass spectrometry yields significantly higher accuracy for the diagnosis and differential diagnosis of CRC. [ABSTRACT FROM AUTHOR]

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Adenostemma lavenia is a perennial herb belonging to the Compositae family and is widely distributed in the tropical parts of Asia. It has been widely used as medicine in Taiwan with the whole plant used to treat pulmonary congestion, pneumonia, bacterial infections of the respiratory tract, edema, and inflammation. This study sought to investigate the anti-inflammatory effects of A. lavenia in vitro and in animal models. The anti-inflammatory effects of ethyl acetate fractions of A. lavenia (EAAL) were stimulated with lipopolysaccharide (LPS) murine macrophages (RAW 264.7) and lung injury in mice. EAAL reduced proinflammatory cytokine responses. Preoral EAAL alleviated LPS-induced histological alterations in lung tissue and inhibited the infiltration of inflammatory cells and protein concentrations in bronchoalveolar lavage fluid (BALF). EAAL prevented protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2); phosphorylation of I κ B- α , MAPKs, and AMP-activated protein kinase (AMPK); and activated anti-oxidant enzymes (catalase, SOD, and GPx), heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) in LPS-stimulated cells and lung tissues. Fingerprinting of EAAL was performed with HPLC to control its quality, and p -coumaric acid was found to be a major constituent. This study suggests that EAAL is a potential therapeutic agent to treat inflammatory disorders. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate the in-use physicochemical and biological stability of the Sandoz rituximab biosimilar, marketed under the trade names Rixathon® and Riximyo® in the European Union, upon preparation for intravenous infusion. Methods Three batches of Rixathon®/Riximyo® in the final month of their 36 month shelf life were exposed to room temperature and light for 14 days to recapitulate a major temperature excursion. Samples were diluted to the lowest allowable concentration of 1 mg/mL in 0.9% NaCl solution in either polypropylene or polyethylene infusion bags and stored for 14 or 30 days at 5 ± 3℃ followed by an additional 24 h at room temperature to simulate product handling. Samples stored in infusion bags were analyzed using SEC, CEX, non-reducing CE-SDS, peptide mapping and CDC to assess physicochemical and biological stability. Results Analysis of Rixathon®/Riximyo® diluted to the lowest allowable concentration in 0.9% sodium chloride in either polypropylene or polyethylene infusion bags revealed no change in molecular weight variants, charge variants, deamidation, oxidation, overall composition or potency over a 31-day period. Conclusion Physicochemical and biological analyses demonstrate that Rixathon®/Riximyo® stability is not impacted by dilution and formulation conditions required for intravenous infusion, even under worst case conditions with regard to product shelf life, temperature excursion, light exposure, dilution factor and infusion bag storage time over a 31-day period. [ABSTRACT FROM AUTHOR]