Amperometric alcohol electrode with extended linearity and reduced interferences.

Conventional amperometric alcohol electrodes were constructed with oxygen- and hydrogen peroxide-base sensors and a much improved electrode was designed by placing a hydrophobic, gas-permeable membrane over the conventional hydrogen peroxide-based alcohol electrode. The immobilization of alcohol oxidase with glutaraldehyde was also studied and optimized. The upper linear ranges of the conventional and newly designed alcohol electrodes were 0.02 and 0.5% ethanol, respectively. The hydrophobic membrane of the new design eliminated the classical electrochemical interferences of hydrogen peroxide-based electrodes and the typical pH dependence of enzymatic systems.     

Uptake by corn and chemical extractability of heavy metals from a four year compost treated soil

This paper gives the results from four-year field experiments on compost application, added at the maximum rate allowed by Italian legislation (30 t/ha/y). The purpose of the experiment was to evaluate any eventual heavy metal accumulation in soil and corn plants. Cadmium in corn plants increased particularly in the roots from 0.22 mg kg⁻¹ to 1.31 mg kg⁻¹, concentration of Zn and Cu increased in grains, from 26.8 to 35.8 and from 2.4 to 4.2 mg kg⁻¹ respectively. Relevant increase in the roots was detected for Zn from 34.6 to 146.8 mg kg⁻¹. Only in the 4th year Ni concentration increases in the root portion while the content of Pb and Cr in corn was generally unaffected by the compost application. Heavy metals in the soil determined by a sequential chemical extraction, indicated that extractability changed with time. A certain increase was found from the beginning to the end of the experiment particularly for Zn, from 23.3 mg kg⁻¹ to 45.1 mg kg⁻¹ in extractable forms. Nevertheless the extractable amounts are rather small in respect to the total heavy metal content of compost.     

Estrogen receptors: new perspectives in breast cancer management

The imbalance between proliferative and differentiative estrogenic effect, caused by quantitative and qualitative alteration of the estrogen receptor (ER) expression, may play a determinant role in mammary neoplastic transformation. Our studies demonstrate that ER levels are significantly higher in human mammary neoplastic tissues when compared to perineoplastic tissues and that increased ER expression is associated with ER gene hypomethylation. During progressive multifactorial carcinogene, ER overexpression may represent an early step in neoplastic transformation. In fact, high levels of ER represent good markers of differentiation and can predict the likelihood of benefiting from anti-estrogen therapy. Nevertheless, about 35% of ER-positive breast cancers are resistant to endocrine therapy and 10% of ER-negative tumors behave as hormone-sensitive tumors. Recent studies on ER mRNA variants, which naturally occur in human breast tumors, demonstrated mutations, deletions and alternative splicings, yielding deletions of exons 3, 4, 5 and 7. ER variants exhibited altered functions or changed the responsiveness to hormonal therapy. Analysis of these variants could be a useful parameter to better predict tumor responsiveness to anti-estrogen therapy. Recently, a regain of hormonal responsiveness by ER-negative breast cancer cells has been reported following ER gene transfection. However, estradiol treatment inhibits rather than stimulates cell growth as well as the metastatic and invasive potential of the ER gene transduced cells. Transfer of the ER gene may be considered as a new therapeutic approach in the management of hormone-independent breast cancer.     

The Degradation of Romanowsky-Type Blood Stains in Methanol

The oxidative demethylation of Romanowsky-type stains in methanol has been examined quantitatively with respect to its effect upon the staining of blood smears. Spectral changes in hound dye, observed through two color filters, have been measured for the nuclei and cytoplasm of segmented neutrophils and monocytes utilizing the LARC™ automated differential analyzer. Stain decomposition in methanol results in a large loss in staining intensity with little change in color. The loss in intensity has been correlated with the observed spectral changes in the degraded stain. High-performance liquid chromatographic analysis of degraded stain samples has shown the products of methanolic degradation to be different from those obtained in aqueous polychroming reactions. To maintain a stain of defined thiazine dye composition and thus defined staining properties, refrigeration is recommended.     

Attenuation of SARS‐CoV‐2 replication and associated inflammation by concomitant targeting of viral and host cap 2'‐O‐ribose methyltransferases

The SARS‐CoV‐2 infection cycle is a multistage process that relies on functional interactions between the host and the pathogen. Here, we repurposed antiviral drugs against both viral and host enzymes to pharmaceutically block methylation of the viral RNA 2''‐O‐ribose cap needed for viral immune escape. We find that the host cap 2''‐O‐ribose methyltransferase MTr1 can compensate for loss of viral NSP16 methyltransferase in facilitating virus replication. Concomitant inhibition of MTr1 and NSP16 efficiently suppresses SARS‐CoV‐2 replication. Using in silico target‐based drug screening, we identify a bispecific MTr1/NSP16 inhibitor with anti‐SARS‐CoV‐2 activity in vitro and in vivo but with unfavorable side effects. We further show antiviral activity of inhibitors that target independent stages of the host SAM cycle providing the methyltransferase co‐substrate. In particular, the adenosylhomocysteinase (AHCY) inhibitor DZNep is antiviral in in vitro, in ex vivo, and in a mouse infection model and synergizes with existing COVID‐19 treatments. Moreover, DZNep exhibits a strong immunomodulatory effect curbing infection‐induced hyperinflammation and reduces lung fibrosis markers ex vivo. Thus, multispecific and metabolic MTase inhibitors constitute yet unexplored treatment options against COVID‐19.     

LOX-1, a new marker of risk and prognosis in coronary artery disease?

The development of atherosclerosis is caused by the accumulation of lipid, inflammatory cytokine production, and the large amount of inflammatory cells in the arterial wall. It is now established that the presence of oxidized low-density lipoproteins (ox-LDL) has an important role in the pathogenesis of the disease. There are many scavenger receptors for ox-LDL, among which LOX-1 seems to be important for the induction of endothelial dysfunction and the other subsequent events that lead to the formation of atheromatous plaque. Our findings indicate the presence of a regulatory role induced by the presence of ox-LDL on LOX-1 through the amplification of IL-6 synthesis. This mechanism contributes to the upregulation of the ORL-1 gene expression in presence of risk factors. Many authors have shown the possibility to use LOX-1 as a good marker for the diagnosis and prognosis of coronary artery disease because it is easy to measure and more sensitive than other markers commonly used in the routine of laboratory medicine.     

In vivo antimalarial activity of novel 2-hydroxy-3-anilino-1,4-naphthoquinones obtained by epoxide ring-opening reaction

1,4-Naphthoquinone derivatives are known to have relevant activities against several parasites. Among the treatment options for malaria, atovaquone, a 1,4-naphthoquinone derivative, is widely applied in the treatment and prophylaxis of such disease. Based on the structure simplification of atovaquone, we designed and synthesized four novel naphthoquinoidal derivatives. The compounds were obtained by the underexplored epoxide-opening reaction of 1,4-naphthoquinone using aniline derivatives as nucleophiles. The antiplasmodial activity of the synthesized compounds was performed in vivo using Peter’s 4 days suppression test. Significant parasitemia reduction and increased survival were observed for some of the compounds.     

Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology

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Biogenic synthesis of silver nanoparticles using Brazilian propolis

Biological methods have been used to synthesize silver nanoparticles through materials such as bacteria, fungi, plants, and propolis due to their reducing properties, stabilizer role and environmentally friendly characteristic. Considering the antimicrobial activity of propolis as well as the broad-spectrum antibacterial effects of silver nanoparticles, this study aim to describe the use of Brazilian propolis to synthesize silver nanoparticles (AgNP-P) and investigate its antimicrobial activity. The synthesis was optimized by factorial design, choosing the best conditions for smaller size particles. AgNP-P demonstrated a maximum absorbance at 412 nm in ultraviolet-visible spectra, which indicated a spherical format and its formation. Dynamic light scattering demonstrated a hydrodynamic size of 109 nm and polydispersity index less than 0.3, showing a good size distribution and stability. After its purification via centrifugation, microscopy analysis corroborates the format and showed the presence of propolis around silver nanoparticle. X-ray diffraction peaks were attributed to the main planes of the metallic silver crystalline structure; meanwhile infrared spectroscopy demonstrated the main groups responsible for silver reduction, represented by ∼22% of AgNP-P indicates by thermal analysis. Our product revealed an important antimicrobial activity indicating a synergism between propolis and silver nanoparticles as expected and promising to be an effective antimicrobial product to be used in infections.     

Utilization of acetonitrile and other aliphatic nitriles by a Candida famata strain

Abstract A variant of a yeast strain identified as Candida famata isolated from gold mine effluent was able to grow on acetonitrile, acrylonitrile, butyronitrile, isobutyronitrile, methacrylnitrile, propionitrile, succinonitrile, valeronitrile, acetamide, isobutyamide, and succinamide as sole nitrogen source, after acclimatization. The yeast grew on acetonitrile and acetamide at concentrations up to 4%. The utilisation of acetonitrile and acetamide by the C. famata strain probably involves hydrolysis in a two-step reaction mediated by both inducible and intracellular nitrile hydratase and amidase.