Cell-penetrating peptides (CPPs) are a group of peptides, which have the ability to cross cell membrane bilayers. CPPs themselves can exert biological activity and can be formed endogenously. ...Fragmentary studies demonstrate their ability to enhance transport of different cargoes across the blood-brain barrier (BBB). However, comparative, quantitative data on the BBB permeability of different CPPs are currently lacking. Therefore, the in vivo BBB transport characteristics of five chemically diverse CPPs, i.e. pVEC, SynB3, Tat 47-57, transportan 10 (TP10) and TP10-2, were determined. The results of the multiple time regression (MTR) analysis revealed that CPPs show divergent BBB influx properties: Tat 47-57, SynB3, and especially pVEC showed very high unidirectional influx rates of 4.73 μl/(g × min), 5.63 μl/(g × min) and 6.02 μl/(g × min), respectively, while the transportan analogs showed a negligible to low brain influx. Using capillary depletion, it was found that 80% of the influxed peptides effectively reached the brain parenchyma. Except for pVEC, all peptides showed a significant efflux out of the brain. Co-injection of pVEC with radioiodinated bovine serum albumin (BSA) did not enhance the brain influx of radiodionated BSA, indicating that pVEC does not itself significantly alter the BBB properties. A saturable mechanism could not be demonstrated by co-injecting an excess dose of non-radiolabeled CPP. No significant regional differences in brain influx were observed, with the exception for pVEC, for which the regional variations were only marginal. The observed BBB influx transport properties cannot be correlated with their cell-penetrating ability, and therefore, good CPP properties do not imply efficient brain influx.
Paclitaxel and nanoparticle albumin-bound paclitaxel are known to cause adverse events of eye disorders, such as cystoid macular edema. However, at present, the risk factors remain unclear. ...Therefore, risk factors for eye disorders caused by paclitaxel and nanoparticle albumin-bound paclitaxel were studied. This retrospective study targeted patients who were newly administered paclitaxel or nanoparticle albumin-bound paclitaxel at Kyoto Okamoto Memorial Hospital between April 1, 2012, and March 31, 2017. Eye disorder occurrence was defined as an event in which the pharmacist confirmed the symptoms in a patient interview and the ophthalmologist diagnosed the disorder. To analyze the risk factors, logistic regression analysis using 41 factors was performed. Of 128 subjects, 13 (10.2%) had eye disorders with symptom degrees of Grades 1 and 2. The symptoms were conjunctivitis or subconjunctival hemorrhage (3.1%), visual acuity reduction (2.3%), blurred vision and eye pain (1.6% each), eye mucus, blepharitis, stye, watering eyes, photopsia, and muscae volitantes (0.8% each). In eight patients, the conditions patients improved with spontaneously or with medication use; no improvements were observed the cases of visual acuity reduction, blurred vision, or muscae volitantes. Multivariate logistic regression analysis revealed that a cumulative dose of ≥819 mg/m2 (odds ratio: 5.34, 95% confidence interval: 1.32–21.60, p=0.019) and baseline alkaline phosphatase ≥256 U/L (odds ratio: 3.74, 95% confidence interval: 1.02–13.70, p=0.046) were significant risk factors associated with eye disorders. In conclusion, it was determined that paclitaxel- and nanoparticle albumin-bound paclitaxel-related eye disorders might be influenced by cumulative dose and baseline alkaline phosphatase.
Tubulointerstitial abnormalities are predictive of the progression of diabetic kidney disease (DKD), and their targeting may be an effective means for prevention. Proximal tubular (PT) expression of ...kidney injury molecule (KIM)-1, as well as blood and urinary levels, are increased early in human diabetes and can predict the rate of disease progression. Here, we report that KIM-1 mediates PT uptake of palmitic acid (PA)-bound albumin, leading to enhanced tubule injury with DNA damage, PT cell-cycle arrest, interstitial inflammation and fibrosis, and secondary glomerulosclerosis. Such injury can be ameliorated by genetic ablation of the KIM-1 mucin domain in a high-fat-fed streptozotocin mouse model of DKD. We also identified TW-37 as a small molecule inhibitor of KIM-1-mediated PA-albumin uptake and showed in vivo in a kidney injury model in mice that it ameliorates renal inflammation and fibrosis. Together, our findings support KIM-1 as a new therapeutic target for DKD.
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•KIM-1 is expressed in proximal tubules of humans with diabetic kidney disease•KIM-1 mediates the endocytic uptake of palmitic acid (PA)-bound albumin•KIM-1-mediated PA-albumin uptake leads to interstitial inflammation and fibrosis•TW-37 prevents KIM-1-mediated PA-albumin uptake and ameliorates tubular injury
Mori et al. report that during diabetic kidney disease KIM-1 mediates proximal tubular uptake of palmitic acid-bound albumin, leading to enhanced tubule injury with interstitial inflammation and fibrosis, as well as secondary glomerulosclerosis. Further, they identify a small molecule inhibitor of KIM-1, TW-37, that can ameliorate the injury.
Amaç: C-reaktif protein/albümin oranı (CAO) yakın zamanda yeni bir inflamatuar biyobelirteç olarak tanımlanmış ve inflamasyonun belirlenmesinde birçok hastalıkta potansiyel rolü ortaya konulmuştur. ...Bu çalışma, aksiyel spondiloartritte (axSpA) hastalık aktivitesinin belirlenmesinde CAO’nun rolünü araştırmayı amaçlamaktadır. Gereç ve Yöntem: Bu çalışma retrospektif vaka-kontrol çalışmasıdır. Toplam 128 hasta ve 111 yaş-cinsiyet uyumlu sağlıklı kontrol çalışmaya dahil edilmiştir. Serum albumin, C-reaktif protein (CRP), eritrosit sedimantasyon hızı (ESH) kaydedildi. CAO, serum CRP/Albumin şeklinde hesaplanmıştır. Hastalık aktivitesini belirlemek için Bath Ankilozan Spondilit Hastalık Aktivite İndeksi (BASDAI) ve Ankilozan Spondilit Hastalık Aktivite Skoru-CRP (ASDAS-CRP) skorları kullanıldı. Hastalar ASDAS-CRP skoruna göre iki alt gruba ayrıldı: ≥1,3 aktif hastalık,
Objective: The C-reactive protein/albumin ratio (CAR) has recently emerged as a novel inflammatory biomarker, indicating its potential role in determining inflammation in various disorders. This study aims to investigate the role of CAO in determining disease activity in axial spondyloarthritis (axSpA). Materials and Methods: This study is a retrospective case-control study. A total of 128 patients with axSpA and 111 age-gender-matched healthy controls were included in the study. Serum albumin, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were recorded. CAR was calculated as serum CRP/Albumin. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) scores were used to determine disease activity. Patients were divided into two subgroups based on the ASDAS-CRP score: ≥1.3 was considered active disease, and
Provider: - Institution: - Data provided by Europeana Collections- Cranach (Lucas). Passional, cité- Held (Caspar). Album amicorum (1564)- Numérisation effectuée à partir d'un document original.- Cet ...album est formé d'un exemplaire de l'Antithesis de Simon Du Rosier et d'un certain nombre de feuillets intercalés.Voici d'abord la description du volume imprimé :Antithesis || De præclaris Christi || et indignis || Papæ facinoribus, || ⁂ || Cum decalogis vtriusque oppositis, cúmque || amborum morum descriptione : quemad- || modum sancta Scriptura tradit. || Per Zachariam Durantium. || 1558. S. l. Genève, in-8 de 7 p. non chiffr. et 88 p. chiffr.Le titre porte la marque de Z. Durand, avec la devise : Non accenditur lucerna ut sub modio, sed ut in candelabro ponatur Matth. V (Silvestre, 11° 1075). — Au v° du titre, SIMONIS ROSARII Tetrastichon.Au fol. A ii est une épître en distiques de Simon Du Rosier « Illustrissimis viris senatorii ordinis, Joanni Steghel, celeberrimae urbis Bernae quaestori, et Hieronymo Manueli, Lausanae praefecto ».Les ff. A iij et A iiij r° sont occupés par un avis de l'imprimeur au lecteur : « Zacharias Durantius typographus lectori. »L'ouvrage, écrit en distiques, commence au fol. A iiij v°, d'où part la pagination. Il se compose de 18 chapitres ou antithèses opposant les faits du Christ à ceux du pape. Le texte est orné de 36 figures admirablement gravées sur bois, que l'on attribue, au moins celles qui se rapportent à la vie du Christ, à Bernard Salomon, dit le Petit Bernard. L'artiste s'est inspiré des planches du Passional de Lucas Cranach. L'imprimeur s'est efforcé de placer en regard l'image du Christ et celle du pape. Le volume se termine par un morceau en prose : De praestantissimis Christi et indignissimis Antichristi moribus viri fidelis Declaratio lectori.D'après La France protestante (nouv. éd., V, col. 1057) l'édition qui vient d'être décrite est la seconde. Elle ne porte pas en tête de l'épître dédicatoire les mots : Studio Simonis Rosarii. Le même recueil résume le peu que l'on sait de la vie de Du Rosier. Nous ajouterons seulement que, d'après un dizain de lui, imprimé en tête du Droit Chemin de musique de Loys Bourgeois (1550), il était alors « bachelier », c'est-à-dire sous-maitre au collège de Rive à Genève (Alfred Cartier, Arrêts du conseil de Genève de 1541 à 1550, 1893, p. 152).Le propriétaire du livre, Caspar Held, « Waldseensis », a couvert presque toutes les marges du volume de notes écrites en latin et en allemand. Il y a de plus ajouté un grand nombre de feuillets qui ont reçu, ou des notes, ou des inscriptions dues à des amis qui étudiaient la théologie à Tübingen en 1564.Au v° du f. actuellement coté 1 sont les armes de Caspar Held : de ? à un sinistrochère tenant un bâton d'Esculape placé en pal et duquel issent une branche de laurier (?) et une croix. Les pièces de l'écu se retrouvent dans le cimier entre deux proboscides.Au r° du f. 2 se lisent deux épigrammes latines de Held, In Catalogum amicorum ; au v° de ce même f. commence la table : Catalogus amicorum et fautorum, qui se termine au r° du fol. 3. On y trouve 43 noms ; mais il n'y en a en réalité que 42, l'un des noms figurant deux fois.De ces inscriptions, 22 seulement nous ont été conservées, les feuillets qui terminaient primitivement le volume ayant été perdus. Voici la liste de ces 22 noms :Beutler (Thomas), « Rauenspurgensis », Tübingen, 25 février 1564, fol. 43,Bienemann (Kaspar), dit Melissander, Tübingen, 10 mars 1564, fol. 24. — Né à Nuremberg en 1540, surintendant général à Altenbourg, il a laissé des poésies latines. Il mourut en 1591. Sa vie a été publiée par J. H. Aker en 1718.Fabricius. Voy. Schmidt.Georg (Johann), « Georgii », Tübingen, 2 février 1564, fol. 75.Heyperger (Karl), Tübingen, 11 mars 1564, fol. 82.Holtzer (Johann), Tübingen, 10 mars 1564, fol. 84.Jäger (Esaias), « Venator, Boiiloncarinanus », s. d., fol. 22.Kiermer (Sebastian), de Ratisbonne, s. d., fol. 77.Kirchmeir (Eustachius), Tübingen, 22 août 1564, fol. 106.Krapf (Peter), d'Oppenheim, s. d., fol. 28.Kupferschmid (Jakob), Tübingen, 5 mai 1564, fol. 47.Melissander. Voy. Bienemann.Münster (Ludwig), « Bisecaniensis », 21 juillet 1564, fol. 52.Oesterreicher (Wenzel Christoph), 1564, fol. 81 v°.Raab (Jakob), « Rabus », de Strasbourg, fils de Ludwig, Tübingen, 4 janvier 1564, fol. 13. — Converti au catholicisme en 1570, Johann Jakob Raab fit connaître sa résolution par une lettre adressée à son père et devint un ardent polémiste.Raupach (Johann), « ex Silesiorum civitate Leoberga », Tübingen, 11 février 1564, fol. 86.Reichardt (Christoph), « Neuburgensis », Tübingen, 13 septembre 1564, fol. 14. (Armes dessinées. Parti : au l de ? à un membre d'aigle de ? ; au 2 de ? au même membre d'aigle les serres placées en l'air. Cimier : un vol chargé des pièces de l'écu.)Schmidt (Johann), « Fabricius, Campidonensis », 1564, fol. 48 v°.Schopper (Jakob), « Biberacensis », 1564, fol. 45.Silberborner (Georg), de Worms, 3 mai 1564, fol. 79 v°. (Devise : Moyen par tout.)Spiller (Marcus), « Austriacus », Tübingen, 23 février 1564, fol. 81.Sudels (Georg), 4 mars 1564, fol. 65. (A la table le nom est écrit Zudels.)Venator. Voy. Jäger.Weckerlin (Jakob), « Calvuensis », 1564, fol. 69.Wildtperger (Georg), de Linz, Tübingen, 11 mars 1564, fol. 39.La table placée en tête du volume (fol. 2 v°-3) nous a conservé les noms de plusieurs personnages qui s'étaient inscrits dans l'album, mais dont les inscriptions ont disparu. En voici la liste :Brentl (Christoph), « Dichopolitanus ».Einkirch (Peter).Einodt (Crispinian).Elephant (V.), « Elephas ».Engelscald (Paul).Heusinger (Andreas).Holder (Wilhelm). — C'est l'auteur de plusieurs ouvrages de polémique virulente contre les calvinistes.Holpp (Ulrich).Meier (Jakob).Planck (Martin), « Plancus », de Linz. (Le nom figure deux fois à la table.Schey (Urban), « Wickersheimensis ».Schulthaiss (Martin).Schulz (Friedrich), de Stuttgart.Schwin (Andreas Emerich).Sieder (Urban).Stürzelig (Johann), « Holczheimensis ».Vay (Gutpert), « Tubingensis ».Wimpelin (Burckhard).Zeycht (Konrad), « Munderkhingensjs ».Zimmermann (Wilhelm).Au XVIIe siècle le volume était entre les mains de JOHANN WALTHER HELD, qui a recueilli un certain nombre d'inscriptions nouvelles et qui a surchargé de sentences et de passages bibliques presque tous les espaces restés vides. Voici la table des inscriptions :Bantzer (Hans Jörg), d'Augsbourg, Ulm, 4 septembre 1635, fol. 90. — Un Christoph Bantzer, orfèvre à Augsbourg, fut membre du grand conseil de cette ville en 1649 et mourut en 1653 (Marc Rosenberg, Der Goldschmiede Merkzeichen, 1911, p. 75).Bloss (Johann), Ulm, 25 août 1635, fol. 73.Bombarter (Anton), Ulm, 23 août 1635, fol. 73 v°.Dockel (Georg), « physicus et medicinae doctor reipublicae », Ulm, octobre 1635, fol. 73 v°.Eberlin (Hans Jakob), 30 août 1635, fol. 88 v°.Ehrke (?) (Johann Bapt.), de Worms, Ulm, 25 août 1635, fol. 90 v°.Held (Johann Baptist), avocat, Ulm, 9 août 1635 ; mort en 1636, fol. 79Herseburg (Gottfried Friedrich von), Ulm, 25 août 1635, fol. 65 v°.Honold (Jakob), professeur de logique. Ulm, 30 octobre 1635, fol. 86 v°. — C'est peut-être le Jakob Honold à qui on doit deux opuscules sur les comètes, imprimés à Ulm, en 1681, in-4 : Monitor hominum novissimus, das ist Kurtzer Bericht von dem ungewöhnlich grossen Cometen..., et Novus hominum Excitator.Horst (Gregor), « reipublicae ulmensis archiater », Ulm, 12 août 1635, fol. 6 V. Horst est l'auteur de divers ouvrages médicaux imprimés à Wittenberg et à Ulm.Köllin (David), Ulm, 28 octobre 1635, fol. 88 v°.Köllin (Wolfgang), Ulm, 22 septembre 1635, fol. 90 v°.Merckh (Johann Chunrad), maître d'école à Ulm, Ulm, 31 octobre 1635, fol. 84 v°.Pfanner (Johann), « Viennensis, medicinae doctor », Ulm, 23 octobre 1635, fol. 75 v°.Rulich (Jakob), « Ruohlich », prédicateur protestant, Ulm, septembre 1635, fol. 7 v°. — Jakob est probablement l'auteur de la Leich-Predig auf dess Menschen Absterben, imprimée en 1658, à Heidelberg, à la suite de l'Homo novus de Peter von Streithagen.Schwehrburg (Johann Constantin Wilhelm Freiherr von), 3 août 1636, fol. 62 v°.Thoner (Augustin), « medicinae doctor et physicus », Ulm, ex musaeo, 11 août 1635, fol. 73. — Thoner est l'auteur d'Observationes et d'Epistolae medicinales, imprimées à Ulm en 1651 et 1653. Quelques-unes de ses observations ont été insérées par Bonnet dans sa Bibliothèque de médecine, t. IV (1708, in-4).Villing (Johann R.), Ulm, 1er novembre 1635, fol. 82 v°.Visscher (Christoph), Ulm, 17 septembre 1635, fol. 50.La dernière mention de Johann Walther Held est datée de 1660.- Cranach (Lucas). Passional, cité- Devises et anagrammes : Moyen par tout, Georg Sylberborner, de Worms (1564).- Devises et anagrammes : Non accenditur lucerna ut sub modio, sed ut in candelabro ponatur, Zacharie Durand, imprimeur à Genève (1558).- Held (Caspar). Album amicorum (1564)- Manuscrits de la collection James de Rothschild.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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•A new nanosensor based on BSA capped-CuNCs for MGF detection was developed.•The proposed nanosensor showed excellent performance in sensing of MGF.•The mechanism of the selective ...recognition of MGF by the CuNCs@BSA sensor was proposed.•The nanosensor was applied in real samples with good recoveries.
In this paper we report for the first time a fluorescence nanosensor for the detection of trace amount of mangiferin (MGF) by using bovine serum albumin (BSA)-protected copper nanoclusters (CuNCs@BSA). The CuNCs@BSA have an average size of 1.4±0.2nm and show a blue emission at 640nm. Fluorescence emission of CuNCs@BSA was quenched in the presence of MGF providing a fluorescence responsive probe in a linear range of 3–180μM with a detection limit of 210nM calculated at a signal-to-noise ratio of 3. The CuNCs@BSA show high photostability, since after 50min of irradiation, only a fluorescence decrease of 15% is appreciated. Interference and competition studies indicate that the nanoprobe presents good selectivity over other relevant molecules including flavonoids and metal ions. These results confirmed that the nanosensor has high selectivity towards MGF in the presence of other substances. In addition the mechanism of sensitive fluorescence quenching response of CuNCs@BSA to MGF has been discussed. The sensor was then applied to the analysis of MGF in African mango extract and satisfactory recoveries were obtained indicating a good accuracy and reproducibility of the fluorescence nanosensor for detection of MGF. The proposed sensor is simple, rapid, and cost-effective demonstrating great potential for the determination of MGF in real samples.
Bovine serum albumin (BSA) was firstly implemented as an effective sensitivity enhancer for a peptide-based amperometric biosensor for the ultrasensitive detection of prostate specific antigen (PSA). ...A porous and conductive substrate of chitosan-lead ferrocyanide-(poly(diallyldimethylammonium chloride)-graphene oxide) was in-situ generated on a glassy carbon electrode (GCE), in which Pb2Fe(CN)6 served as a novel redox species with strong current signal at −0.46 V (vs. Ag/AgCl). Poly(diallyldimethylammonium chloride)-graphene oxide was applied to improve conductivity of the substrate. After adsorbing Pb2+ for signal amplification, chitosan provided active sites to simultaneously immobilize peptides and 1-aminopropyl-3-methylimidazolium chloride by glutaraldehyde. To enhance the sensitivity, BSA was chemically linked to the immobilized peptide, behaving as a serious decrease of current signal for BSA hindering the electron transfer. The dramatic increase of current signal of the biosensor was obtained by PSA cleaving the immobilized BSA-peptide. The proposed biosensor exhibited a detection limit of 1fgmL−1 for PSA and its sensitivity was seven-fold higher than previous works.
•BSA was firstly implemented as an effective sensitivity enhancer for the peptide-based amperometric biosensor.•Multiple amplification strategies were developed for the amperometric biosensor for PSA.•Chitosan-Pb2Fe(CN)6-PDDA-GO as a new redox species was used as substrate.
Abstract Human serum albumin (HSA) is a biological nanocarrier that forms non-covalent complexes with a number of synthetic and biomolecules. Previously we demonstrated radiolabeled HSA-based ...nanoparticles can form non-covalent complexes with fluorescent cyanine dyes yielding imaging agents for surgical guidance towards tumor draining lymph nodes. Here the self-assembly approach enabled rapid clinical translation. Based on this experience we reasoned it would be interesting to expand this non-covalent technology to a targeted approach. Therefore, the ability of HSA to form non-covalent self-assembled complexes with peptides via near-infrared (NIR) cyanine dyes was explored. Föster resonance energy transfer (FRET) quenching interactions between HSA-Cy5 and the non-covalently bound fluorescent molecules indocyanine green (ICG), IR783–CO2 H and three IR783-labeled targeting peptides were used to monitor complex assembly and disassembly. The host-guest interactions between HSA and IR783-labeled peptides enabled the formation of (bio)nanoparticles that are coated with peptides, which may target αv β3 -integrins, the chemokine receptor 4 (CXCR4), or somatostatin receptors. The potential of CXCR4-targeted (bio)nanoparticles in sentinel lymph node procedures is demonstrated in vivo. By non-covalently binding NIR-dye labeled peptides to an already clinically approved HSA-scaffold, we have readily formed targeted bionanoparticles.
Purpose
This paper aims to investigate the immunoinhibitory properties of a lymph nodes-targeting suppressive oligonucleotide (ODN) for the potential treatment of autoimmune diseases or chronic ...inflammation.
Methods
Synthetic suppressive ODN engineered with an albumin-binding diacyl lipid at the 5′-terminal (lipo-ODN) was synthesized.
In vitro
and
in vivo
experiments were designed to compare the immune suppressive properties of lipo-ODN and unmodified ODN. Cellular uptake and distribution, inhibition of Toll-like receptor (TLR) activation, lymph nodes (LN) draining, and the suppression of antigen-specific immune responses in an ovalbumin protein model was investigated.
Results
Compared to unmodified ODN, lipid functionalized suppressive ODN demonstrated enhanced cellular uptake and TLR-9 specific immune suppression in TLR reporter cells. Additionally, injection of a low dose of lipid-modified suppressive ODN, but not the unconjugated ODN, accumulated in the draining LNs and exhibited potent inhibition of antigen-specific CD8
+
T cell and B cell responses
in vivo
.
Conclusions
Targeting suppressive ODN to antigen presenting cells (APCs) in the local LNs is an effective approach to amplify the immune modulation mediated by ODN containing repetitive TTAGGG motif. This approach might be broadly applicable to target molecular adjuvants to the key immune cells in the LNs draining from disease site, providing a simple strategy to improve the efficacy of many molecular immune modulators.
The effective removal of heavy metals and soluble microbial products from wastewater is crucial for ensuring a safe environment and good quality human health. The present work investigated the ...potential of eggshell (ES) waste as an adsorbent for removing heavy metals and soluble microbial products. ES was firstly used to capture heavy metal ions, and the eggshell–metal (ES-M) complex was then applied to remove soluble microbial products (e.g., proteins) from aqueous solution. In this study, bovine serum albumin (BSA) was selected as a model protein-based contaminant. The equilibrium and kinetic characteristics of soluble protein removed by ES were evaluated in batch mode involving parameters such as metal ions (Cu
2+
, Zn
2+
, Ni
2+
, Co
2+
), operating temperatures (277–323 K), and particle size of ES (100–700 µm). The isotherm curves were well-fitted by Langmuir–Freundlich model. As the temperature increased from 277 to 323 K, the maximum binding capacity for BSA increased from 25.22 to 34.28 (mg BSA/g ES-Zn). The negative values of Δ
G
° indicated the spontaneous nature of the protein adsorption, while the kinetic of protein adsorption followed the pseudo-second-order model. ES functionalized with heavy metal ions acted as an effective pseudo-chelating adsorbent for the removal of soluble protein from wastewater. Chelates of Zn–BSA found on the ES complexes were found to be highly stable, indicating a minimal possibility of secondary pollution caused by these Zn- and BSA-containing ES complexes. The ES-Zn complex can be potentially used as an adsorbent for removing soluble microbial products in wastewater prior to the membrane filtration.
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