Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.     

Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase and Other Targets for the Inhibition of Cancer Cell Proliferation

Digoxin is a cardiac glycoside long used to treat congestive heart failure and found recently to show antitumor potential. The hydroxy groups connected at the C-12, C-14, and C-3′a positions; the C-17 unsaturated lactone unit; the conformation of the steroid core; and the C-3 saccharide moiety have been demonstrated as being important for digoxin’s cytotoxicity and interactions with Na⁺/K⁺-ATPase. The docking profiles for digoxin and several derivatives and Na⁺/K⁺-ATPase were investigated; an additional small Asn130 side pocket was revealed, which could be useful in the design of novel digoxin-like antitumor agents. In addition, the docking scores for digoxin and its derivatives were found to correlate with their cytotoxicity, indicating a potential use of these values in the prediction of the cancer cell cytotoxicity of other cardiac glycosides. Moreover, in these docking studies, digoxin was found to bind to FIH-1 and NF-κB but not HDAC, IAP, and PI3K, suggesting that this cardiac glycoside directly targets FIH-1, Na⁺/K⁺-ATPase, and NF-κB to mediate its antitumor potential. Differentially, digoxigenin, the aglycon of digoxin, binds to HDAC and PI3K, but not FIH-1, IAP, Na⁺/K⁺-ATPase, and NF-κB, indicating that this compound may target tumor autophagy and metabolism to mediate its antitumor propensity.     

Evaluation of the Long‐term Cumulative UVA Facial Exposure of Queensland School Teachers derived for an Extended Period from the OMI Satellite Irradiance

This research presents a novel methodology for deriving the total daily broadband solar UVA (320–400 nm) received by school teachers during their working day from Ozone Monitoring Instrument (OMI) satellite solar noon UVA irradiance measurements for a Queensland subtropical site (27.5°S, 152°E). Daily UVA exposures are weighted to the anatomical human cheek (anterior infra‐orbital region) for teachers wearing and not wearing broad‐brimmed hats. The method utilizes the OMI UVA irradiance data collected daily at high temporal resolution over 2005 to 2016 to derive the total daily UVA exposure to a horizontal plane. These horizontal plane exposures are scaled by factors to take into account the timing of outdoor activity. The relationship between exposures to a horizontal plane and those to a vertical plane and the protection provided by a broad‐brimmed hat was assessed to evaluate the total daily UVA exposures to the cheek for classroom and physical education teaching staff expected to be outside at different periods of the day. The developed method enables the total daily UVA exposure to specific anatomical sites to be evaluated from the satellite solar noon irradiance at locations that do not have access to surface‐based instrumentation capable of recording in the solar UVA waveband.     

A rugged landscape model for self-organization and emergent leadership in creative problem solving and production groups

The process by which an initially leaderless group differentiates into one containing leadership and secondary role structures was examined using the swallowtail catastrophe model and principles of selforganization. The objectives were to identify the control variables in the process of leadership emergence in creative problem solving groups and production groups. In the first of two experiments, groups of university students (total N = 114) played a creative problem solving game. Participants later rated each other on leadership behavior, styles, and variables related to the process of conversation. A performance quality measure was included also. Control parameters in the swallowtail catastrophe model were identified through a combination of factor analysis and nonlinear regression. Leaders displayed a broad spectrum of behaviors in the general categories of Controlling the Conversation and Creativity in their role-play. In the second experiment, groups of university students (total N = 197) engaged in a laboratory work experiment that had a substantial production goal component. The same system of ratings and modeling strategy was used along with a work production measure. Leaders in the production task emerged to the extent that they exhibited control over both the creative and production aspects of the task, they could keep tension low, and the externally imposed production goals were realistic.     

Dielectric studies of the 4-n-alkyl-4'-thiocyanatobiphenyl (nBT) homologous series (n=2-10) in the isotropic and E phases

Results of the dielectric studies of nine members of the nBT (4-n-alkyl-4'-thiocyanatobiphenyl, n= 2-10) homologous series in the crystal E (E) and isotropic (I) phases are presented. The dependence of the static permittivity ?_s in the isotropic phase, the longitudinal relaxation times τ_is and τ_∥, and the activation enthalpies ΔH _is and ΔH _∥ on the number of carbon atoms in the alkyl chain n are analysed. A considerable increase in the retardation factor g= τ_∥/τ_is with decreasing n is observed. The results are compared with those obtained for similar two-ring homologous series. The parameters characterizing the molecular rotations around the short axis in the E phase (τ_∥ and ΔH _∥) indicate a hardening of this solid-like phase with shortening of the alkyl chain.     

Spontaneous formation of liquid crystalline phases and phase transitions in highly concentrated plasmid DNA

The liquid crystalline (LC) properties of two supercoiled plasmid DNA samples, pBSK (2958 bp) and pGEM (3000 bp), have been studied using polarised light microscopy (PLM), circular dichroism (CD) and UV–Vis spectroscopy. The influence of methods of isolation on plasmid LC behaviour is described, and using PLM we have demonstrated the spontaneous formation of cholesteric fingerprint-like textures. Preliminary studies of LC phase transitions in pGEM show the irreversibility of LC phase formation, as a consequence of changes in the tertiary structure of supercoiled plasmids. Using UV–Vis spectroscopy a hyperchromic effect was observed with increasing temperature. The CD spectra clearly showed structural changes, and probably mismatching of DNA bases, during cooling. Finally, we have observed an irreversible phase transition in plasmid DNA which is very different from that previously reported in linear DNA.     

Application of Sulfinyl bis(2,4‐dihydroxythiobenzoyl) in the Synthesis of N‐Substituted 2‐Amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles

One‐stage synthesis of N‐substituted 2‐amino‐5‐(2,4‐dihydroxyphenyl)‐1,3,4‐thiadiazoles is described. The compounds were prepared by the reaction of the sulfinyl bis(2,4‐dihydroxythiobenzoyl) (STB) with 4‐substituted 3‐thiosemicarbazides. STB was obtained from 2,4‐dihydroxybenzenecarbodithioic acid and thionyl dichloride. The structure of compounds was confirmed by IR, ¹H NMR, ¹³C NMR, and EI‐MS data.     

Efficient One‐Pot Synthesis of a Densely Functionalized Tetrahydropyridine in the Presence of [1,1′‐Binaphthalene]‐2,2′‐diol/Indium(III) Chloride (binol/InCl3) or Simple Brønsted Acids as Catalysts

The highly functionalized tetrahydropyridine 4 was obtained in an indium(III) chloride catalyzed multi‐component reaction from benzaldehyde, 4‐methoxyaniline, and ethyl acetoacetate (=ethyl 3‐oxobutanoate) in the presence of [1,1′‐binaphthalene]‐2,2′‐diol (binol). It was found that binol played a beneficial role in this reaction, allowing a substantial decrease of the amount of indium salt. Also, simple organic Brønsted acids may serve as effective organocatalysts in this process.     

Ultraviolet Reflection Irradiances and Exposures in The Constructed Environment For Horizontal,Vertical and Inclined Surfaces

Ultraviolet (UV) reflection in the urban constructed environment is not well understood for topical issues such as measuring and modeling the received UV exposure due to that UV reflection for outdoor workers. Both predominantly specular and diffuse reflecting surface types have been identified and investigated for the erythemal UV reflection ratio variation due to solar zenith angle and orientation. This paper presents relationships between erythemal UV reflection ratios measured for non‐horizontal and horizontal surfaces, with predominantly specular surface types indicating stronger relationships with solar zenith angles than diffuse reflecting surfaces types. Erythemal UV exposures caused by the same reflecting surface types at three inclinations are also investigated. Non‐horizontal surfaces can increase erythemal UV exposures compared to erythemal UV exposures received from the same horizontal surface by factors of 1.07–1.46 for specific body sites and by 1.01–1.70 for averages of group body sites for zinc aluminium coated steel sheeting.