Computational Identification of Dithymoquinone as a Potential Inhibitor of Myostatin and Regulator of Muscle Mass

The skeletal muscle (SM) is the largest organ in the body and has tremendous regenerative power due to its myogenic stem cell population. Myostatin (MSTN), a protein produced by SM, is released into the bloodstream and is responsible for age-related reduced muscle fiber development. The objective of this study was to identify the natural compounds that inhibit MSTN with therapeutic potential for the management of age-related disorders, specifically muscle atrophy and sarcopenia. Sequential screening of 2000 natural compounds was performed, and dithymoquinone (DTQ) was found to inhibit MSTN with a binding free energy of −7.40 kcal/mol. Furthermore, the docking results showed that DTQ reduced the binding interaction between MSTN and its receptor, activin receptor type-2B (ActR2B). The global energy of MSTN-ActR2B was found to be reduced from −47.75 to −40.45 by DTQ. The stability of the DTQ–MSTN complex was subjected to a molecular dynamics analysis for up to 100 ns to check the stability of the complex using RMSD, RMSF, Rg, SASA, and H-bond number. The complex was found to be stable after 10 ns to the end of the simulation. These results suggest that DTQ blocks MSTN signaling through ActR2B and that it has potential use as a muscle growth-promoting agent during the aging process.     

Calcium and strontium anthranilato complexes as effective Fusarium moniliforme controlling agents

This paper presents the one‐pot reaction synthesis of coordination calcium and strontium compounds [Ca(L)₂(H₂O)₂ 1 and Sr(L)₂(H₂O)₂ 2 ] with the 2‐(4‐chlorophenylamino) benzoic acid ligand ( HL  = C₁₃H₁₀NO₂Cl). The complexes were obtained in good yields, and their structures were corroborated according to their CHN, spectroscopic (IR and UV/Vis.) and solution molar conductivity data as the latter confirmed their molecular nature. Additionally, the powder X‐ray diffraction pattern of the complexes was used to determine the cell parameters and the hkl indices together with their corresponding 2θ values. The microbial resistance against the currently available antifungal agents requires searching for new antifungal compounds. Promising fungicidal activities of these coordination complexes were determined against the Fusarium corn disease as complexes 1 and 2 at 30°C inhibited the grain pathogenicity by 70% and 66%, respectively. Moreover, 1 and 2 retarded the amylase enzymes that are responsible for the pathogenicity by 35.13% and 26.22% at 30°C.     

7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z Notonipetranone Attenuates Neuropathic Pain by Suppressing Oxidative Stress,Inflammatory and Pro-Apoptotic Protein Expressions

7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid obtained from a natural source has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose-dependent manner. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor-alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing the caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed a protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, the anti-neuropathic potential of ECN might be due to the inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.     

Coefficient estimates for a certain family of analytic functions involving a q-derivative operator

The Ramanujan Journal - In this paper, we study the coefficient estimates for a class of analytic functions defined by using the q-Ruscheweyh derivative operator. In particular, we investigate the...     

Sorption behavior of Sn(II) onto Haro river sand from aqueous acidic solutions

The sorption behavior of Sn(II) onto Haro river sand has been examined with respect to nature of electrolyte, agitation time, dosage of sorbent and concentration of sorbate. Maximum sorption (95.5%) has been achieved from 0.034M hydrochloric acid solution after equilibrating sorbate (2·10⁻⁵M) and sorbent (50 mg) for 120 minutes at aV/W ratio of 90 cm³·g⁻¹. The kinetic data have been subjected to Morris-Weber and Lagergren equations. The kinetics of sorption proceeds a two stage process consisting of a relatively slow initial uptake followed by a much rapid increase in the sorption. The rate constant of intraparticle transport, K_d, comes out to be 8.75·10⁻⁸ mol·g⁻¹·min^−1/2 and the first order rate constant for sorption is 0.0416 min⁻¹. The sorption data of Sn(II) onto Haro river sand followed Langmuir, Freundlich and Dubinin-Radushkevich (D-R) type isotherms. The Langmuir constant,Q, related to sorption capacity and,b, related to sorption energy are computed to be 10.6±1.1 μmol·g⁻¹ and 1123±137 dm³·mol⁻¹, respectively. The D-R isotherm yields the values ofC _m=348±151 μmol·g⁻¹ and β=−0.01044±0.0008 mol²·kJ⁻² and ofE=6.9±0.3 kJ·mol⁻¹. In all three isotherms correlation factor (γ) is ≥0.99. The influence of common anions and cations on the sorption has been investigated. Zn(II), Mg(II), oxalate, Pb(II), Mn(II) and tartrate reduce the sorption significantly whereas Fe(II) causes substantial increase in the sorption. It is essential that all ions causing a decrease in the sorption of Sn(II) must be absent from the sorptive solution otherwise low sorption yields would result.     

A one-step implicit iterative method for two finite families of asymptotically nonexpansive mappings in a hyperbolic space

We introduce a one-step implicit iterative method for two finite families of asymptotically nonexpansive mappings in a hyperbolic space and use it to approximate common fixed points of these families. The results presented in this paper are new in the setting of hyperbolic spaces. On top, these are generalizations of several results in literature from Banach spaces to hyperbolic spaces. At the end of the paper, we give an example to validate our results.     

Pseudo-differential Operators,Cubature and Equidistribution on the 3D ball: An Approach Based on Orthonormal Basis Systems

In this paper, the distribution of points on a unit ball in ?³ is investigated. The ansatz is motivated by an approach for point grids on the unit sphere by Cui and Freeden. A formula for a generalized discrepancy is developed, which is then used to check the uniformity of point grids on a ball. The generalized discrepancy originates from an error bound for a quadrature (cubature) rule on the ball with uniform weights. In particular, we discuss the integration of functions from particular Sobolev spaces based on known orthonormal systems on the ball. This includes the introduction of a concept of pseudo-differential operators on the ball. Finally, different point grids are constructed on the ball and are compared by the discrepancy. Furthermore, numerical and graphical comparisons of the grids are presented.     

Untargeted Phytochemical Profile,Antioxidant Capacity and Enzyme Inhibitory Activity of Cultivated and Wild Lupin Seeds from Tunisia

Lupin seeds can represent a valuable source of phenolics and other antioxidant compounds. In this work, a comprehensive analysis of the phytochemical profile was performed on seeds from three Lupinus species, including one cultivar (Lupinus albus) and two wild accessions (Lupinus cossentinii and Lupinus luteus), collected from the northern region of Tunisia. Untargeted metabolomic profiling allowed to identify 249 compounds, with a great abundance of phenolics and alkaloids. In this regard, the species L. cossentinii showed the highest phenolic content, being 6.54 mg/g DW, followed by L. luteus (1.60 mg/g DW) and L. albus (1.14 mg/g DW). The in vitro antioxidant capacity measured by the ABTS assay on seed extracts ranged from 4.67 to 17.58 mg trolox equivalents (TE)/g, recording the highest values for L. albus and the lowest for L. luteus. The DPPH radical scavenging activity ranged from 0.39 to 3.50 mg TE/g. FRAP values varied between 4.11 and 5.75 mg TE/g. CUPRAC values for lupin seeds ranged from 7.20 to 8.95 mg TE/g, recording the highest for L. cossentinii. The results of phosphomolybdenum assay and metal chelation showed similarity between the three species of Lupinus. The acetylcholinesterase (AChE) inhibition activity was detected in each methanolic extract analyzed with similar results. Regarding the butyrylcholinesterase (BChE) enzyme, it was weakly inhibited by the Lupinus extracts; in particular, the highest activity values were recorded for L. albus (1.74 mg GALAE/g). Overall, our results showed that L. cossentinii was the most abundant source of polyphenols, consisting mainly in tyrosol equivalents (5.82 mg/g DW). Finally, significant correlations were outlined between the phenolic compounds and the in vitro biological activity measured, particularly when considering flavones, phenolic acids and lower-molecular-weight phenolics.     

DFT study of acceleration of electrocyclization in photochromes under radical cationic conditions: Comparison with recent experimental data

Radical cation formation is proposed for the rapid cyclization of 1, 2-bis[5-phenyl-2-methylthien-3-yl]cyclopentene and oligothiophene functionalized dimethyldihydropyrenes (DMDHP). Density functional theory calculations have been performed to rationalize the effect of a radical cation on the activation barrier of different classes of electrocyclic photochromes (DHP, dithienylethene, dihydroazulene and fulgide). For exact comparative analysis, the activation barrier of neutral (singlet) analogues at the same level of theory are also calculated. In addition, the concerted nature and aromaticity of transition states were investigated with the help of synchronicity (Sy.) and nuclear independent chemical shift values NICS(0) calculations, respectively, for both the radical cation and neutral systems. In case of the radical cation, thermal return of CPD to DHP, the activation barrier is very low (ΔH = 3.13 kcal mol^?1, ΔG = 4.01 kcal mol^?1) as compared to the neutral analogue (ΔH = 20.6 kcal mol^?1, ΔG = 20.98 kcal mol^?1), which is consistent with experimental observations. Similarly for dithenylethenes, radical cation formation has a large impact on the activation barrier (ΔH = 19.44 kcal mol^?1, ΔG = 22.29 kcal mol^?1). However, radical cation formation has almost negligible impact on the activation barrier of VHF-DHA and fulgide isomerization. The significant difference has been observed for synchronicity and NICS(0) values of all types of photochromes under radical cation conditions as compared to the neutral system.     

Chemical and structural characterization of α-N-acetylgalactosaminidase I and II from starfish, <Emphasis Type="Italic">asterina amurensis</Emphasis>

Background

The marine invertebrate starfish was found to contain a novel α-N-acetylgalactosaminidase, α-GalNAcase II, which catalyzes removal of terminal α-N-acetylgalactosamine (α-GalNAc), in addition to a typical α-N-acetylgalactosaminidase, α-GalNAcase I, which catalyzes removal of terminal α-N-acetylgalactosamine (α-GalNAc) and, to a lesser extent, galactose. The interrelationship between α-GalNAcase I and α-GalNAcase II and the molecular basis of their differences in substrate specificity remain unknown.

Results

Chemical and structural comparisons between α-GalNAcase I and II using immunostaining, N-terminal amino acid sequencing and peptide analysis showed high homology to each other and also to other glycoside hydrolase family (GHF) 27 members. The amino acid sequence of peptides showed conserved residues at the active site as seen in typical α-GalNAcase. Some substitutions of conserved amino acid residues were found in α-GalNAcase II that were located near catalytic site. Among them G171 and A173, in place of C171 and W173, respectively in α-GalNAcase were identified to be responsible for lacking intrinsic α-galactosidase activity of α-GalNAcase II. Chemical modifications supported the presence of serine, aspartate and tryptophan as active site residues. Two tryptophan residues (W16 and W173) were involved in α-galactosidase activity, and one (W16) of them was involved in α-GalNAcase activity.

Conclusions

The results suggested that α-GalNAcase I and II are closely related with respect to primary and higher order structure and that their structural differences are responsible for difference in substrate specificities.