Elucidation of mechanisms of action of Wei-Sheng-Fang-Yi-Bao-Dan in the treatment of COVID-19 and depression using network pharmacology and molecular docking

Purpose: To investigate the mechanisms of action of Wei-Sheng-Fang-Yi-Bao-Dan (WSFYBD) in the treatment of COVID-19 and depression using network pharmacology and molecular docking. Methods: First, the bioactive components and target genes of WSFYBD were retrieved from TCMSP database. The relevant gene targets of depression and COVID-19 were obtained from databases. The core WSFYBD genes for treatment were separately obtained by determining gene intersection. Cytoscape 3.8.0 software was used to draw the visual interactive networks. STRING database was employed to construct protein-protein interaction networks, while Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were used to determine the function and pathway of target genes via a Bioconductor/R. Finally, AutoDockTools software was employed for molecular docking. Results: A total of 105 potential bio-active components and 35 target genes of WSFYBD for COVID-19 therapy were identified. Also, 1905 GO entries (p < 0.05) and 158 related signal pathways (p < 0.05) for COVID-19 were obtained. Similarly, 114 potential bio-active components of WSFYBD and 127 potential therapeutic targets of depression were identified. Moreover, 1948 GO entries (p < 0.05) and 177 related signal pathways for depression were retrieved (p < 0.05). Docking results showed the main bio-active components were closely bound to the core targets. Conclusion: The mechanisms for treating COVID-19 show that WSFYBD directly acts on SARS-CoV-2 virus to prevent it from entering the host cell, or inhibits virus replication. Secondly, WSFYBD ameliorates depression by acting on key targets that control over-activated cytokines. Therefore, WSFYBD has potentials for the management of COVID-19 and depression

Valley-dependent gauge fields for ultracold atoms in square optical superlattices

We propose an experimental scheme to realize the valley-dependent gauge fields for ultracold fermionic atoms trapped in a state-dependent square optical lattice. Our scheme relies on two sets of Raman laser beams to engineer the hopping between adjacent sites populated by two-component fermionic atoms. One set of Raman beams are used to realize a staggered \pi-flux lattice, where low energy atoms near two inequivalent Dirac points should be described by the Dirac equation for spin-1/2 particles. Another set of laser beams with proper Rabi frequencies are added to further modulate the atomic hopping parameters. The hopping modulation will give rise to effective gauge potentials with opposite signs near the two valleys, mimicking the interesting strain-induced pseudo-gauge fields in graphene. The proposed valley-dependent gauge fields are tunable and provide a new route to realize quantum valley Hall effects and atomic valleytronics.Comment: 5+ pages, 2 figures; language polished, references and discussions added; accepted by PR

Quantum simulation of exotic PT-invariant topological nodal loop bands with ultracold atoms in an optical lattice

Since the well-known PT symmetry has its fundamental significance and implication in physics, where PT denotes the combined operation of space-inversion P and time-reversal T, it is extremely important and intriguing to completely classify exotic PT-invariant topological metals and to physically realize them. Here we, for the first time, establish a rigorous classification of topological metals that are protected by the PT symmetry using KO-theory. As a physically realistic example, a PT-invariant nodal loop (NL) model in a 3D Brillouin zone is constructed, whose topological stability is revealed through its PT-symmetry-protected nontrivial Z2 topological charge. Based on these exact results, we propose an experimental scheme to realize and to detect tunable PT-invariant topological NL states with ultracold atoms in an optical lattice, in which atoms with two hyperfine spin states are loaded in a spin-dependent 3D OL and two pairs of Raman lasers are used to create out-of-plane spin-flip hopping with site-dependent phase. Such a realistic cold-atom setup can yield topological NL states, having a tunable ring-shaped band-touching line with the two-fold degeneracy in the bulk spectrum and non-trivial surface states. The states are actually protected by the combined PT symmetry even in the absence of both P and T symmetries, and are characterized by a Z2-type invariant (a quantized Berry phase). Remarkably, we demonstrate with numerical simulations that (i) the characteristic NL can be detected by measuring the atomic transfer fractions in a Bloch-Zener oscillation; (ii) the topological invariant may be measured based on the time-of-flight imaging; and (iii) the surface states may be probed through Bragg spectroscopy. The present proposal for realizing topological NL states in cold atom systems may provide a unique experimental platform for exploring exotic PT-invariant topological physics.Comment: 11 pages, 6 figures; accepted for publication in Phys. Rev.

Anti-inflammatory effects of bitongling granules are mediated through the suppression of miR-21/p38 MAPK/TLR4/NF-κB signaling in H9C2 rat cardiac cells exposed to lipopolysaccharides

Purpose: To assess the protective effects of bitongling granules on H9C2 cells exposed to lipopolysaccharides (LPS) in the management of rheumatoid arthritis (RA)-induced myocardial inflammation.Methods: The effects of bitongling granule (BTLG) drug-containing serum were assessed in myocarditis models established in rat cardiac cells. MicroRNA-21 (miR-21) levels were evaluated by qRT-PCR while MTT assays were performed to assess cell viability. ELISA assay was used to evaluate tumor necrosis factor α (TNF-α), interleukin 17 (IL-17) and interleukin 6 (IL-6) levels in cell culture supernatants. Apoptosis was determined by flow cytometry (FCM). Quantitative mitogen-activated protein kinase (MAPK)/p38, toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB)/p65 levels were evaluated by western blot and immunofluorescenceResults: BTLG increased cardiac cell activity and exhibited anti-inflammatory effect. It also inhibited LPS-induced H9C2 apoptosis and suppressed p65 NF-κB phosphorylation (p-p65 NF-κB), TLR4, and p38 MAPK phosphorylation (p-p38 MAPK). BTLG also reduced miR-21 expression, and the overexpression of the miR-21 inhibitor in H9C2 suppressed apoptosis. Moreover, p-p38 MAPK, TLR4 and p-p65 NF-κB expression were down-regulated in miR-21 inhibitor transfected H9C2s. The inhibition of p38/TLR4/ NF-κB signaling might have occurred via the suppression of miR-21 by BTLG.Conclusion: The results show that BTLG inhibits the inflammatory reaction involved in p38MAPK/TLR4/ NF-κB signaling pathway and can prevent RA-induced cardiac disease, suggesting that BTLP treatment may be beneficial for the management of arthritic cardiomyopathy

Selenite reduction by the obligate aerobic bacterium <i>Comamonas testosteroni</i> S44 isolated from a metal-contaminated soil

BACKGROUND: Selenium (Se) is an essential trace element in most organisms but has to be carefully handled since there is a thin line between beneficial and toxic concentrations. Many bacteria have the ability to reduce selenite (Se(IV)) and (or) selenate (Se(VI)) to red elemental selenium that is less toxic. RESULTS: A strictly aerobic bacterium, Comamonas testosteroni S44, previously isolated from metal(loid)-contaminated soil in southern China, reduced Se(IV) to red selenium nanoparticles (SeNPs) with sizes ranging from 100 to 200 nm. Both energy dispersive X-ray Spectroscopy (EDX or EDS) and EDS Elemental Mapping showed no element Se and SeNPs were produced inside cells whereas Se(IV) was reduced to red-colored selenium in the cytoplasmic fraction in presence of NADPH. Tungstate inhibited Se(VI) but not Se(IV) reduction, indicating the Se(IV)-reducing determinant does not contain molybdenum as co-factor. Strain S44 was resistant to multiple heavy and transition metal(loid)s such as Se(IV), As(III), Cu(II), and Cd(II) with minimal inhibitory concentrations (MIC) of 100 mM, 20 mM, 4 mM, and 0.5 mM, respectively. Disruption of iscR encoding a transcriptional regulator negatively impacted cellular growth and subsequent resistance to multiple heavy metal(loid)s. CONCLUSIONS: C. testosteroni S44 could be very useful for bioremediation in heavy metal(loid) polluted soils due to the ability to both reduce toxic Se(VI) and Se(IV) to non-toxic Se (0) under aerobic conditions and to tolerate multiple heavy and transition metals. IscR appears to be an activator to regulate genes involved in resistance to heavy or transition metal(loid)s but not for genes responsible for Se(IV) reduction

Poly(ADP-ribose) Polymerase 1 Is Indispensable for Transforming Growth Factor-β Induced Smad3 Activation in Vascular Smooth Muscle Cell

BACKGROUND: Transforming growth factor type-β (TGF-β)/Smad pathway plays an essential role in vascular fibrosis. Reactive oxygen species (ROS) generation also mediates TGF-β signaling-induced vascular fibrosis, suggesting that some sort of interaction exists between Smad and redox pathways. However, the underlying molecular mechanism is largely unknown. This study aims to investigate the influence of poly(ADP-ribose) polymerase 1 (PARP1), a downstream effector of ROS, on TGF-β signaling transduction through Smad3 pathway in rat vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: TGF-β1 treatment promoted PARP1 activation through induction of ROS generation in rat VSMCs. TGF-β1-induced phosphorylation and nuclear accumulation of Smad3 was prevented by treatment of cells with PARP inhibitor, 3-aminobenzamide (3AB) or N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino)acetami (PJ34), or PARP1 siRNA. TGF-β1 treatment promoted poly(ADP-ribosy)lation of Smad3 via activation of PARP1 in the nucleus. Poly(ADP-ribosy)lation enhanced Smad-Smad binding element (SBE) complex formation in nuclear extracts and increased DNA binding activity of Smad3. Pretreatment with 3AB, PJ34, or PARP1 siRNA prevented TGF-β1-induced Smad3 transactivation and expression of Smad3 target genes, including collagen Iα1, collagen IIIα1 and tissue inhibitor of metalloproteinase 1, in rat VSMCs. CONCLUSIONS: PARP1 is indispensable for TGF-β1 induced Smad3 activation in rat VSMCs. Targeting PARP1 may be a promising therapeutic approach against vascular diseases induced by dysregulation of TGF-β/Smad3 pathway

dc-europe bulletin no. 1974.9

Published by Groupe democrate-chrétien du Parlement europée

Poly[diethyl­enetriammonium [aquadi-μ2-sulfato-sulfatolanthanum(III)]]

In the title compound, {(C4H16N3)[La(SO4)3(H2O)]}n, the La atom adopts an irregular LaO9 coordination geometry, including one bonded water mol­ecule. The three sulfate groups adopt both monodentate and bidentate coordination to the metal ions. Two of the sulfate groups serve as bridges in the (100) and (010) directions, yielding infinite sheets, whereas the third is pendant to one La3+ cation. The protonated organic species inter­acts with the layers by way of N—H⋯O hydrogen bonds, and O–H⋯O hydrogen bonds involving aqua ligands also occur