Insulin Resistance Associated Genes and miRNAs

Type 2 diabetes mellitus is the result of resistance to insulin function along with inadequate insulin secretion, leading to a number of dysfunctions characterized by hyperglycemia, and it is associated with microvascular, macrovascular, and neuropathic complications. There is compelling evidence that the decline in both insulin sensitivity and insulin secretion has a genetic component. In addition, increasing evidence suggests that microRNAs (miRNAs) as key regulators of gene expression play significant roles in insulin production, secretion, and function that regulate the function of insulin-target tissues. The current review demonstrates the candidate genes and the related miRNAs involved in molecular pathogenesis of insulin resistance in type 2 diabetes mellitus. In doing so, it provides an opportunity for more focused investigations that may identify the genes and miRNAs with a role in the pathogenesis of type 2 diabetes mellitus and its treatment.     

Abnormal Association between Metal−Organic Cages and Counterions Regulated by the Hydration Shells

A unique trend in the binding affinity between cationic metal−organic cages (MOCs) and external counteranions in aqueous media was observed. Similar to many macroions, two MOCs, sharing similar structures but carrying different number of charges, self-assembled into hollow spherical single-layered blackberry-type structures through counterion-mediated attraction. Dynamic and static light scattering and isothermal titration calorimetry measurements confirm the stronger interactions among less charged MOCs and counteranions than that of highly charged MOCs, leading to larger assembly sizes. DOSY NMR measurements suggest the significance of thick hydration shells of highly charged MOCs, inhibiting the MOC-counterion binding and weakening the interaction between them. This study demonstrates that the greater role played by hydration shell on ion-pair formation comparing with charge density of MOCs.     

Transmission dynamics of novel coronavirus SARS-CoV-2 among healthcare workers,a case study in Iran

One of the main concerns during the COVID-19 pandemic was the protection of healthcare workers against the novel coronavirus. The critical role and vulnerability of healthcare workers during the COVID-19 pandemic leads us to derive a mathematical model to express the spread of coronavirus between the healthcare workers. In the first step, the SECIRH model is introduced, and then the mathematical equations are written. The proposed model includes eight state variables, i.e., Susceptible, Exposed, Carrier, Infected, Hospitalized, ICU admitted, Dead, and finally Recovered. In this model, the vaccination, protective equipment, and recruitment policy are considered as preventive actions. The formal confirmed data provided by the Iranian ministry of health is used to simulate the proposed model. The simulation results revealed that the proposed model has a high degree of consistency with the actual COVID-19 daily statistics. In addition, the roles of vaccination, protective equipment, and recruitment policy for the elimination of coronavirus among the healthcare workers are investigated. The results of this research help the policymakers to adopt the best decisions against the spread of coronavirus among healthcare workers.

     

Synthesis,characterization, and biological screening of metal complexes of novel sulfonamide derivatives: Experimental and theoretical analysis of sulfonamide crystal

This study reports the synthesis of sulfonamide-derived Schiff bases as ligands L ¹ and L ² as well as their transition metal complexes [VO(IV), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II)]. The Schiff bases (4-{E-[(2-hydroxy-3-methoxyphenyl)methylidene]amino}benzene-1-sulfonamide ( L ¹ ) and 4-{[(2-hydroxy-3-methoxyphenyl)methylidene]amino}-N-(5-methyl-1,2-oxazol-3-yl)benzene-1-sulfonamide ( L ² ) were synthesized by the condensation reaction of 4-aminobenzene-1-sulfonamide and 4-amino-N-(3-methyl-2,3-dihydro-1,2-oxazol-5-yl)benzene-1-sulfonamide with 2-hydroxy-3-methoxybenzaldehyde in an equimolar ratio. Sulfonamide core ligands behaved as bidentate ligands and coordinated with transition metals via nitrogen of azomethine and the oxygen of the hydroxyl group. Ligand L ¹ was recovered in its crystalline form and was analyzed by single-crystal X-ray diffraction technique which held monoclinic crystal system with space group (P2₁/c). The structures of the ligands L ¹ and L ² and their transition metal complexes were established by their physical (melting point, color, yields, solubility, magnetic susceptibility, and conductance measurements), spectral (UV–visible [UV–Vis], Fourier transform infrared spectroscopy, ¹H NMR, ¹³C NMR, and mass analysis), and analytical (CHN analysis) techniques. Furthermore, computational analysis (vibrational bands, frontier molecular orbitals (FMOs), and natural bonding orbitals [NBOs]) were performed for ligands through density functional theory utilizing B3LYP/6-311+G(d,p) level and UV–Vis analysis was carried out by time-dependent density functional theory. Theoretical spectroscopic data were in line with the experimental spectroscopic data. NBO analysis confirmed the extraordinary stability of the ligands in their conjugative interactions. Global reactivity parameters computed from the FMO energies indicated the ligands were bioactive by nature. These procedures ensured the charge transfer phenomenon for the ligands and reasonable relevance was established with experimental results. The synthesized compounds were screened for antimicrobial activities against bacterial (Streptococcus aureus, Bacillus subtilis, Eshcheria coli, and Klebsiella pneomoniae) species and fungal (Aspergillus niger and Aspergillus flavous) strains. A further assay was designed for screening of their antioxidant activities (2,2-diphenyl-1-picrylhydrazine radical scavenging activity, total phenolic contents, and total iron reducing power) and enzyme inhibition properties (amylase, protease, acetylcholinesterase, and butyrylcholinesterase). The substantial results of these activities proved the ligands and their transition metal complexes to be bioactive in their nature.     

Enhanced electronic and nonlinear optical responses of C24N24 cavernous nitride fullerene by decoration with first row transition metals; A computational investigation

The electronic (energy gap and work function) as well as electrical properties (dipole moment, polarizability, and first hyperpolarizabilities) of the first-row transition metals decorated C₂₄N₂₄ cavernous nitride fullerene were explored using DFT calculations. The transition metals are decorated at N4 cavity of C₂₄N₂₄ fullerene. According to our spin polarized computations, the most stable spin state monotonically increases to sextet for Mn@C₂₄N₂₄ and thereafter dropped off gradually to singlet state for Zn@C₂₄N₂₄ system. The findings demonstrate that transition metals can remarkably decrease the HOMO-LUMO energy gap and work function values up to 63% and 21% of bare C₂₄N₂₄, respectively. As can be seen, when the Sc and Ti metals are located above the N4 cavity of fullerene, systems of enhanced static hyperpolarizabilities (β₀) are delivered. These findings might provide an effective strategy to design high performance eletcro-optical materials based on carbon- nitride fullerene.     

MicroRNA-499a-5p Promotes Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to Cardiomyocytes

Since the adult mammalian heart has limited regenerative capacity, cardiac trauma, disease, and aging cause permanent loss of contractile tissue. This has fueled the development of stem cell-based strategies to provide the damaged heart with new cardiomyocytes. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are capable of self-renewal and differentiation into cardiomyocytes, albeit inefficiently. MicroRNAs (miRNAs, miRs) are non-coding RNAs that have the potential to control stem cell fate decisions and are employed in cardiac regeneration and repair. In this study, we tested the hypothesis that overexpression of miR-499a induces cardiomyogenic differentiation in BM-MSCs. Human BM-MSCs (hBM-MSCs) were transduced with lentiviral vectors encoding miR-499a-3p or miR-499a-5p and analyzed by immunostaining and western blotting methods 14 days post-transduction. MiR-499a-5p-transduced cells adopted a polygonal/rod-shaped (myocyte-like) phenotype and showed an increase in the expression of the cardiomyocyte markers α-actinin and cTnI, as cardiogenic differentiation markers. These results indicate that miR-499a-5p overexpression promotes the cardiomyogenic differentiation of hBM-MSCs and may thereby increase their therapeutic efficiency in cardiac regeneration.     

Silver–palm pollen nanocomposite exhibits antiproliferative,antioxidant, and proapoptotic properties on MCF-7 breast cancer cells

The aim of the present study is to evaluate the antioxidant and proapoptotic effects of silver–palm pollen (Ag/PP) nanocomposite. The percentage of live cells after treatment with various concentrations of Ag/PP (0, 5, 10, 20, and 40 µM/mL) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. The antioxidant potential of Ag/PP was measured via the scavenging effects of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and molecular analysis. Apoptosis was assessed by morphological analysis, fluorescent dye, and flow cytometry, and its fundamental mechanism studied based on evaluation of Bax and Bcl2 gene expression. Ag/PP nanocomposite suppressed the viability of MCF-7 cells (dose and time dependently) and showed antioxidant properties. Morphological changes associated with cell death were observed in treated cells. Accumulation of dead cells in sub-G1 phase confirmed the occurrence of apoptosis in exposed cells. In addition, NPs induced cell death by altering Bcl-2 expression in MCF-7 cells. These results indicate that Ag/PP nanocomposite is an effective combination for removal of cancer cells by induction of apoptosis and could be useful for human health due to its antioxidant effects.     

Antioxidant potential assessment of phenolic and flavonoid rich fractions of Clematis orientalis and Clematis ispahanica (Ranunculaceae)

The antioxidant activities of crude extract fractions using Hexane, Chloroform, Ethyl Acetate, Butanol and Water of Clematis orientalis and Clematis ispahanica were investigated. 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay and the ferric reducing/antioxidant potential (FRAP) were used to evaluate the antioxidant capacity. The total phenolics were found to be 4.37–9.38 and 1.32–11.37 mg gallic acid equivalents (GAE)/g in different fractions for C. orientalis and C. ispahanica, respectively. The ethyl acetate fraction of C. orientalis and chloroform fraction of C. ispahanica showed the highest DPPH and FRAP activities at a concentration of 300 μg/mL. The predominant phenolic compounds identified by HPLC in C. orientalis were Resorcinol (603.5 μg/g DW) in chloroform fraction and Ellagic acid (811.7 μg/g DW) in chloroform fraction of C. ispahanica.     

Synthesis of nanostructured titania/zirconia membrane and investigation of its physical separation and photocatalytic properties in treatment of textile industries wastewater

Nanostructured TiO₂/ZrO₂ composite membranes with varying compositions were obtained by sol–gel technique. The influence of 0–30 mol% zirconia doping on microstructure, water permeability, photocatalytic and physical separation properties, removal of methyl violet of textile industries wastewater and thermal and mechanical stability of titania/zirconia composite membranes was described. Firstly, alumina supports were coated with TiO₂ intermediate layers using the colloidal sol–gel route. The TiO₂/ZrO₂ composite sols were prepared via a polymeric sol–gel method and dip-coated on TiO₂ intermediate layer. The samples were characterized by DLS, TG-DTA, XRD, FTIR, BET-BJH, UV–visible, SEM, TEM and AFM. It was shown that zirconia retards the phase transformation of anatase to rutile until at least 700 °C. The minimum pore size and maximum surface area obtained were 1.2 nm and 153 m²/g, respectively, attributed to the sample with 20 mol% zirconia. The mechanical strength of titania membranes was significantly improved by addition of zirconia. The most methyl violet removal efficiency obtained, with and without UV-irradiation, is 80.8 and 72.6%, respectively, attributed to the sample with 20 mol% zirconia.     

Synthesis of spiro[5.4]decenones and their transformation into bicyclo[4.4]deca-1,4-dien-3-ones by domino "elimination- double-Wagner-Meerwein-rearrangement" reactions

The [3+3] cyclization of 1,3-bis-silyl enol ethers with 1,1-diacylcyclopentanes allows a convenient synthesis of spiro[5.4]decenones. Treatment of these compounds with trifluoroacetic acid (TFA) afforded a great variety of bicyclo[4.4.0]deca-1,4-dien-3-ones containing an angular alkyl group. This core structure occurs in a number of pharmacologically relevant natural products.