AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.     

Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis,Complexing Abilities and Antiproliferative Properties

Background: Dehydropeptides are analogs of peptides containing at least one conjugate double bond between α,β-carbon atoms. Its presence provides unique structural properties and reaction centre for chemical modification. In this study, the series of new class of dipeptides containing S-substituted dehydrocysteine with variety of heterocyclic moieties was prepared. The compounds were designed as the building blocks for the construction of artificial metalloenzymes (artzymes). Therefore, the complexing properties of representative compounds were also evaluated. Furthermore, the acknowledged biological activity of natural dehydropeptides was the reason to extend the study for antiproliferative action of against several cancer cell lines. Methods: The synthetic strategy involves glycyl and phenylalanyl-(Z)-β-bromodehydroalanine as a substrate in one pot addition/elimination reaction of thiols. After deprotection of N-terminal amino group the compounds with triazole ring were tested as complexones for copper(II) ions using potentiometric titration and spectroscopic techniques (UV-Vis, CD, EPR). Finally, the antiproliferative activity was evaluated by sulforhodamine B assay. Results and Conclusions: A simple and efficient procedure for preparation of dipeptides containing S-substituded dehydrocysteine was provided. The peptides containing triazole appeared to be strong complexones of copper(II) ions. Some of the peptides exhibited promising antiproliferative activities against number of cancer cell lines, including cell lines resistant to widely used anticancer agent.     

The Plants of the Asteraceae Family as Agents in the Protection of Human Health

The Asteraceae family is one of the largest flowering plant families, with over 1600 genera and 2500 species worldwide. Some of its most well-known taxa are lettuce, chicory, artichoke, daisy and dandelion. The members of the Asteraceae have been used in the diet and for medicine for centuries. Despite their wide diversity, most family members share a similar chemical composition: for example, all species are good sources of inulin, a natural polysaccharide with strong prebiotic properties. They also demonstrate strong antioxidant, anti-inflammatory and antimicrobial activity, as well as diuretic and wound healing properties. Their pharmacological effects can be attributed to their range of phytochemical compounds, including polyphenols, phenolic acids, flavonoids, acetylenes and triterpenes. One such example is arctiin: a ligand with numerous antioxidant, antiproliferative and desmutagenic activities. The family is also a source of sesquiterpene lactones: the secondary metabolites responsible for the bitter taste of many plants. This mini review examines the current state of literature regarding the positive effect of the Asteraceae family on human health.     

Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF_2α and 1,15-PGF_2α lactones, many 1,15-lactones of E₂, E₃, F₂, F₃, A₂, and A₃ were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

Intrinsic Defect Limit to the Growth of Orthorhombic HfO2 and (Hf,Zr)O2 with Strong Ferroelectricity: First-Principles Insights

It is believed that promoting the fraction of ferroelectric orthorhombic phase (o-phase) through O-poor growth conditions can increase the spontaneous polarization of HfO₂ and (Hf,Zr)O₂ thin films. However, the first-principles calculations show that the growth may be limited by the easy formation of point defects in the orthorhombic and tetragonal phases of HfO₂, ZrO₂, and (Hf,Zr)O₂. Their dominant defects, O interstitial (O_i) under O-rich conditions and O vacancy (V_O) under O-poor condition, have low formation energies and quite high density (10¹⁶–10¹⁹ cm⁻³ for 800–1400 K growth temperature). Especially, O_i has negative formation energy in tetragonal HfO₂ under O-rich condition, causing non-stoichiometry and limiting the crystalline-seed formation during o-phase growth. High-density defects can cause disordering of dipole moments and increase leakage current, both diminishing the polarization. These results explain the experimental puzzle that the measured polarization is much lower than the ideal value even in O-poor thin films and highlight that controlling defects is as important as promoting the o-phase fraction for enhancing ferroelectricity. The O-intermediate condition (average of O-rich and O-poor conditions) and low growth temperature are proposed for fabricating HfO₂ and (Hf,Zr)O₂ with fewer defects, lower leakage current, and stronger ferroelectricity, which challenges the belief that O-poor condition is optimal.     

Enhanced photocatalytic and antifungal activity of ZnO–Cu2+and Ag@ZnO–Cu2+ materials

Zinc oxide is one of the most versatile nanostructured materials with a broad range of applications. Besides, its physicochemical properties can be tuned easily by synthesis conditions to be optimal for a specific application. In our group, we aim for the production of visible light-active materials with enhanced antimicrobial activity. Thus, we synthesize ZnO–Cu²⁺and Ag@ZnO–Cu²⁺ by using a fast and robust microwave solvothermal reaction. We investigate the limit of solubility of Cu²⁺into ZnO lattice producing Cu doped ZnO materials with different doping levels (1, 2, 3, 4, and 5 at. %, Cu/Zn). We also investigate the role of the copper precursor, using copper(II) acetate or copper(II) sulfate as model precursors. Copper acetate incorporates more efficiently into ZnO lattice by decreasing the Eg value of the doped materials at low doping levels. Furthermore, we study the composites Ag@ZnO–Cu²⁺ aiming to reduce doping levels and to improve antimicrobial activity. Characterization of the materials by different techniques demonstrates their uniform size, purity, crystallinity, and visible light activity. In this study, we evaluate airborne fungal contamination and demonstrate the capacity of ZnO–Cu²⁺ and Ag@ZnO–Cu²⁺ to inhibit fungal growth. We studied the microbiological quality of indoor air (vivarium) by sampling air under different conditions. By sampling air with a photocatalytic prototype, the amount of fungi in the air decreases considerably, particularly fungi that can enter the lung. In addition, ZnO–Cu²⁺ shows excellent antifungal activity against Candida sp at low doses. We use Atomic force microscopy (AFM) and holotomographic microscopy (HTM) to provide further evidence on the capacity of the prepared materials to achieve effective damage to fungal cells and to inhibit biofilm formation.     

Preparation of P(St-NMA) microsphere inks and their application in photonic crystal patterns with brilliant structural colors

Patterned photonic crystals with structural colors on textile substrates have attracted a special attention due to the great advantages in application, which currently become a research hot-spot. This study utilized an ink-jet printing technology to prepare high-quality photonic crystal patterns with structural colors on polyester substrates. The self-assembly temperature of poly(styrene-N-methylol acrylamide) (P(St-NMA)) microspheres set to construct photonic crystals were deeply optimized. Moreover, the structural colors of prepared photonic crystal patterns were characterized and evaluated. When the mass fraction of P(St-NMA) microspheres was 1.0 wt.%, the pH value ranged from 5 to 7, and the surface tension was in the range of 63.79 to 71.20 mN/m, inks could present the best print performance. At 60 °C, prepared P(St-NMA) microsphere inks were good for printing to obtain patterned photonic crystals with regular arrangement and beautiful structural colors. Specifically, photonic crystals with different colors could be constructed by regulating the diameter of microspheres in inks, and prepared structural colors exhibited distinct iridescent phenomenon. The present results could provide a theoretical basis for the industrial realization of patterned photonic crystals by ink-jet printing technology.     

Interleukin-1β Modulation of the Mechanobiology of Primary Human Pulmonary Fibroblasts: Potential Implications in Lung Repair

Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1β and used Atomic Force Microscopy to unveil that IL-1β significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1β stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1β may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1β-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1β provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.