A Mini Review on Discovery and Synthesis of Remdesivir as an Effective and Promising Drug against COVID-19

Russian Journal of Bioorganic Chemistry - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as a new human coronavirus has begun spreading over Wuhan City/China in December 2019, and...     

Evaluation of salinity tolerance in sorghum (<Emphasis Type="Italic">Sorghum bicolor</Emphasis> L.) using ion accumulation,proline and peroxidase criteria

Salt tolerance of sorghum varieties in terms of fresh weight, ion accumulations, proline content and peroxidase activity was analyzed in this study. Three sorghum varieties, Payam, Kimia, and Jambo, differing in salt tolerance, were grown in a greenhouse-hydroponic culture with a complete nutrition solution to which 0, 50, 100, 150 and 200 mM NaCl was added. Plant roots and leaves were harvested at 15 and 30 days after treatment and subjected to analysis. Clear decline in K⁺ and Ca²⁺ concentrations and increase in Na⁺ and proline contents were observed in the root and leaf tissues at each NaCl concentration in all varieties during the NaCl treatment. The Ca²⁺ concentration in leaves was higher than in roots, and had the following order in the tested cultivars: Jambo, Kimia, and Payam. Total peroxidase activity increased under salinity stress and it was proportional with the salt concentration. Payam had the largest decrease (46.95%) in fresh weight caused by NaCl, while Jambo had the lowest decrease, 28.63%. Linear regression analysis revealed significant relationships between the estimated factors and fresh weight. The profiles of isoperoxidases were modified under stress conditions. Two isoforms, A1 and A2, were detected in all three varieties with different intensities. Under NaCl stress, isoperoxidases were strongly expressed and a third isoform, A3, was specifically found in variety Jambo suggesting that A3 is implicated in salt adaptation of this variety.     

Annexin C4 in A. fumigatus: a proteomics approach to understand the function

Annexin C4 has been identified as a new member of fungal annexin family. In search of function, we have generated an annexin C4 disruptant strain of human pathogen, Aspergillus fumigatus. Detailed phenotypic analysis confirmed a non essential role of annexin C4 in the growth and sporulation of this pathogen. We applied a comparative proteomics strategy to understand the possible role of this protein in the fungus. The modification of respiratory chain proteins and stress response proteins suggests the occurrence of a mild oxidative stress in anxC4 disruptant strain. This may indicate a possible anti stress function of annexin C4 in A. fumigatus.     

Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials

Background

The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality.

Methods and Findings

This meta-analysis of randomised controlled trials evaluated metformin efficacy (in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal) against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials (13,110 patients) were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio (RR) = 0.99 (95% CI: 0.75 to 1.31), and cardiovascular mortality, RR = 1.05 (95% CI: 0.67 to 1.64). The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR = 0.90 (95% CI: 0.74 to 1.09); all strokes, RR = 0.76 (95% CI: 0.51 to 1.14); heart failure, RR = 1.03 (95% CI: 0.67 to 1.59); peripheral vascular disease, RR = 0.90 (95% CI: 0.46 to 1.78); leg amputations, RR = 1.04 (95% CI: 0.44 to 2.44); and microvascular complications, RR = 0.83 (95% CI: 0.59 to 1.17). For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups (I ² = 41% and 59%). There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction (p = 0.10 and 0.02, respectively).

Conclusions

Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. We cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality. Further studies are needed to clarify this situation. Please see later in the article for the Editors'' Summary     

Proteomics analysis of BHK‐21 cells infected with a fixed strain of rabies virus

Rabies is a neurotropic virus that causes a life threatening acute viral encephalitis. The complex relationship of rabies virus (RV) with the host leads to its replication and spreading toward the neural network, where viral pathogenic effects appeared as neuronal dysfunction. In order to better understand the molecular basis of this relationship, a proteomics study on baby hamster kidney cells infected with challenge virus standard strain of RV was performed. This cell line is an in vitro model for rabies infection and is commonly used for viral seed preparation. The direct effect of the virus on cellular protein machinery was investigated by 2‐DE proteome mapping of infected versus control cells followed by LC‐MS/MS identification. This analysis revealed significant changes in expression of 14 proteins, seven of these proteins were viral and the remaining were host proteins with different known functions: cytoskeletal (capping protein, vimentin), anti‐oxidative stress (superoxide dismutase), regulatory (Stathmin), and protein synthesis (P0). Despite of limited changes appeared upon rabies infection, they present a set of interesting biochemical pathways for further investigation on viral‐host interaction.     

Human primordial germ cells and embryonic germ cells, and their use in cell therapy

Human embryonic germ (hEG) cells derive from the transformation of primordial germ cells (PGCs) under appropriate culture conditions with embryonic fibroblast feeder cells. Although the pluripotent and proliferative capacity of hEG cells is thought to be equivalent to that of human embryonic stem (hES) cells, the difficulties of isolating and maintaining hEG cell lines in vitro have restricted their availability for experimental use. Despite this, some of the factors involved in PGC development, their transformation into embryonic germ cells and the differentiation of embryonic germ cells to specific cell phenotypes have been explored. The potential use of hEG cells in cell therapy applications will, however, depend on a more thorough understanding of how to derive and maintain these cells in vitro.     

Synthesis, characterization, electrochemical and spectroscopic investigation of cobalt(III) Schiff base complexes with axial amine ligands: The layered crystal structure of [Co(salophen)(4-picoline)2]ClO4 · CH2Cl2

Cobalt(III) complexes with potentially tetradentate salophen (H₂salophen = N,N′-bis(salicylidene)-1,2-phenylenediamine) as equatorial ligand and with different axial amine ligands (NH₃, cyclohexylamine, aniline, 4-picoline and pyridine) were synthesized and characterized by IR, ¹H NMR, elemental analysis. Electronic spectra and electrochemical properties of the complexes were studied in DMF solutions. The lowest energy transitions, which occur between 464.8 and 477 nm, are attributed mainly to the intraligand charge transfer, confirmed by Zindo/S electronic structure calculations. The reduction potentials of Co(III)/Co(II) are more affected than those of Co(II)/Co(I) by the axial amine ligands. The crystal structure of the [Co^III(salophen)(4- picoline)₂]ClO₄ · CH₂Cl₂ was determined, indicating that the cobalt(III) center is six coordinated surrounded by the tetradentate salophen ligand and two 4-picoline ligands. The crystal packing of the complex shows a layered structure, in which the perchlorate counter ions and also the lattice solvent molecules are intercalated between the bc planes of the complex cations.     

MicroRNA-7 promotes neural differentiation of trabecular meshwork mesenchymal stem cell on nanofibrous scaffold

The purpose of this study was to investigate miR-7 overexpression effects on neural differentiation of mesenchymal stem cells (MSCs) on both two-dimensional (2D) and three-dimensional (3D) culture systems. We upregulated miR-7 through lentiviral vector in trabecular meshwork MSCs (TMMSCs) and polymers of poly l -lactic acid/polycaprolactone fibrous scaffold were fabricated by electrospinning and characterized using scanning electron microscopy (SEM) and Fourier transform infrared (FTIR). Neural markers expression was evaluated through quantitative-polymerase chain reaction (q-PCR) and immunostaining. The results showed that the high percentage of cell transduction (84.9%) and miR-7 expression (folds: 677.93 and 556.4) was detected in TMMSCs-miR-7(+). SEM and FTIR established the fabrication of the hybrid scaffold. q-PCR analysis showed that on days 14 and 21 of transduction, the expression level of Nestin and glial fibrillary acidic protein (GFAP) genes were significantly higher in the scaffold (3D) compared with tissue culture polystyrene (2D) culture. The expression of microtubule-associated protein-2 (MAP-2) and GFAP genes in TMMSCs-miR-7(+) cells were significantly higher than those miR-7(−) cells after 21 days of cell culture. Also, MAP-2 and Nestin proteins were detected in TMMSCs-miR-7(+) cells. Our results demonstrate that miR-7 is involved in neural differentiation of TMMSCs and scaffold can improve differentiate into glial and neural progenitor cells. These findings provided some information for future use of microRNAs and scaffold in tissue engineering and cell therapy for neurological diseases.     

Alzheimer's disease: immunohistochemical characterization of cerebral amyloid deposits

In Alzheimer cortex tissue sections, thioflavine stained three patterns of amyloid lesions: neurofibrillary tangles (NFT), senile plaques (SP) and vessel walls (amyloid angiopathy AA). An anti serum against Tau proteins detected NFT but neither SP nor AA. In contrast, an anti serum against beta protein amyloid (BP A4) revealed SP and AA but not NFT. A periodic acid pretreatment dramatically enhanced the anti-BP A4 immunolabelling corresponding to microplaques as well as a large amount of diffuse extracellular amyloid substance, but never stained NFT. Pretreatment of tissue sections with a mixture of endo and exoglycosidases gave identical results and corroborates the extraneuronal processing of BP A4 that appears in a glycosylated form in the extracellular compartment.