Cell-free fat extract regulates oxidative stress and alleviates Th2-mediated inflammation in atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease that significantly affects patients’ quality of life. This study aimed to evaluate the therapeutic potential of cell-free fat extract (FE) in AD. In this study, the therapeutic effect of DNCB-induced AD mouse models was investigated. Dermatitis scores and transepidermal water loss (TEWL) were recorded to evaluate the severity of dermatitis. Histological analysis and cytokines measurement were conducted to assess the therapeutic effect. Additionally, the ability of FE to protect cells from ROS-induced damage and its ROS scavenging capacity both in vitro and in vivo were investigated. Furthermore, we performed Th1/2 cell differentiation with and without FE to elucidate the underlying therapeutic mechanism. FE reduced apoptosis and cell death of HaCat cells exposed to oxidative stress. Moreover, FE exhibited concentration-dependent antioxidant activity and scavenged ROS both in vitro and vivo. Treatment with FE alleviated AD symptoms in mice, as evidenced by improved TEWL, restored epidermis thickness, reduced mast cell infiltration, decreased DNA oxidative damage and lower inflammatory cytokines like IFN-γ, IL-4, and IL-13. FE also inhibited the differentiation of Th2 cells in vitro. Our findings indicate that FE regulates oxidative stress and mitigates Th2-mediated inflammation in atopic dermatitis by inhibiting Th2 cell differentiation, suggesting that FE has the potential as a future treatment option for AD

LOSS OF JAK2 REGULATION VIA VHL-SOCS1 E3 UBIQUITIN HETEROCOMPLEX UNDERLIES CHUVASH POLYCYTHEMIA

Chuvash polycythemia (CP) is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the von Hippel-Lindau (VHL) gene whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark features of CP such as hypersensitivity to erythropoietin are unclear. Here, we show that VHL directly binds suppressor of cytokine signalling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated (p)JAK2 for ubiquitin-mediated destruction. In contrast, CP-associated VHL mutants have altered affinity for SOCS1 and fail to engage and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reverses the disease phenotype in vhlR200W/R200W knock-in mice, a model that faithfully recapitulates human CP. These results reveal VHL as a SOCS1-cooperative negative regulator of JAK2 and provide compelling biochemical and preclinical evidence for JAK2- targeted therapy in CP patients

Syntheses and characterization of a series of oxacalix[4]arene-linked cofacial bisporphyrins

A series of oxacalix[4]arene-linked cofacial bisporphyrins 2-4 have been synthesized as free-bases, biszinc(II) and biscopper(II) complexes. UV-vis, fluorescence and cyclic voltammetric studies were performed on the bisporphyrins. Little electronic interactions between the two porphyrin macrocycles in both the metal-free and biszinc(II) complexes 2 and 3 were observed, while enhanced electronic communications were observed in the case of 4 bearing two copper(II) metal ions. Geometry optimizations were carried out using HF/CEP-31G methods to investigate the molecular structures of these bisporphyrins. Solvent effects on the photophysical properties of these bisporphyrins are also discussed. © 2010 World Scientific Publishing Company

Defective graphene on the transition-metal surface: formation of efficient bifunctional catalysts for oxygen evolution/reduction reactions in alkaline media

Supported single-atom catalysts (SACs) have attracted enormous attention because of their high selectivity, activity, and efficiency, compared to conventional nanoparticles and metal bulk catalysts. However, all of these unique merits rely on the stability of the SAC, as reported by many investigators. To avoid aggregation of single-metal atoms and maintain the high performance of the SAC, various substrates have been tried to support them, particularly on graphene nanosheets. A spontaneous interface phenomenon between graphene and the Co (and Ni) substrate discovered in this work is that the holes in the graphene layer can stimulate metal atoms to pop up from a metal substrate and fill the double vacancy in graphene (DV-G) and stabilize on the graphene surface. The unique structure of the lifted metal atom is expected to be useful for the bifunctional SAC for electrocatalytic oxygen evolution reactions (OERs) and oxygen reduction reactions (ORRs). Our first-principles calculations indicate that the DV-G on the Co(0001) surface can serve as an excellent bifunctional OER/ORR catalyst in alkaline media with extremely low overpotentials of 0.39 V for OER and only 0.36 V for ORR processes, which are even lower than those for previously reported bifunctional catalysts. We believe that the catalytic activity stems from the interface coupling effect between the DV-G and metal substrate, as well as the charge redistribution in the graphitic sheet

Hydrogen Activation on the Promoted and Unpromoted ReS₂ (001) Surfaces under the Sulfidation Conditions: A First-Principles Study

Hydrogen activation on the promoted and promoter-free ReS₂(001) surfaces under the sulfidation conditions is studied by means of periodic density function theory (DFT) calculations within the generalized gradient approximation. First, surface-phase diagrams are investigated by plotting the surface free energy as a function of the chemical potential of S (μ_S) on the unpromoted and promoted ReS₂ (001) surfaces with different loadings of nickel, cobalt, tungsten, and tantalum. The results show that on the unpromoted surface sulfur coverage of 25% and on the promoted surfaces sulfur coverage of 25% as well as 25% promoter modification are the most stable conditions, respectively, under hydrodesulfurization (HDS) reaction conditions. Second, hydrogen adsorption and dissociation are explored on these preferred surfaces. It is found that hydrogen adsorbs weakly on all the surfaces studied. The physical adsorption character makes its diffusion favorable, resulting in various adsorption sites and dissociation pathways, i.e., dissociation at surface Re or promote atom, at the interlayer, as well as at the adsorbed S atom. Calculated results show that hydrogen dissociation at the surface Re site is always kinetically favorable. All of the studied dopants can largely activate the adsorbed S but display distinct roles toward the activity of the nearest Re atom; i.e., Co/Ni dopant passivates the nearest surface Re while W/Ta activates it. The activity difference is found to be closely associated with the difference in the bond strength of metal–S and the resultant difference in the induced surface geometry. Moreover, promoter effect is localized because it seems nominal when the reaction occurs at a Re atom with one dopant atom separation. The present results provide a rational understanding of the activity difference between the promoter-free and the promoted surfaces, which would be helpful to further understand the mechanism of HDS and to enhance the development of highly active and selective hydrotreating catalysts

Density Functional Theory Investigation on Thiophene Hydrodesulfurization Mechanism Catalyzed by ReS₂ (001) Surface

We present density functional theory calculations on the reaction mechanism of thiophene hydrodesulfurization (HDS) over ReS₂ (001) surface under typical HDS reaction conditions. It is found that thiophene adopts an “upright” adsorption configuration with the binding energy of 1.26 eV. Considering the factors such as Bader charge, two reaction mechanisms, named direct desulfurization (DDS) to the product of butadiene and hydrogenation (HYD) to 2-butene, 1-butene, and butane, are systematically investigated. Results show that H prefers to attack thiophenic C before the first C–S bond rupture but begins to hydrogenate S_T (S atom of thiophene) after ring-opening. Prehydrogenation has different effect on the activity of C–S bond breaking. When the ring is intact, it has nominal effect; but when the ring is open, appropriate prehydrogenation can dramatically decrease the energy barrier while complete hydrogenation makes the barrier rise again due to stereohindrance effect. The DDS mechanism is proved to be kinetically unfavorable while 2-butene is suggested to be a predominated product for HYD mechanism. The role of S_a (preadsorbed S) is a “ladder” which helps H approach the thiophenic molecule while S_T acts as an “intermediary” for H exchange. Changing reaction conditions through partial pressure of H₂ can only alter the rate-determining step but has nothing to do with the catalytic selectivity