The influence of ABO blood groups on COVID-19 susceptibility and severity: A molecular hypothesis based on carbohydrate-carbohydrate interactions.

The world is experiencing one of the most difficult moments in history with the COVID-19 pandemic, a disease caused by SARS-CoV-2, a new type of coronavirus. Virus infectivity is mediated by the binding of Spike transmembrane glycoprotein to specific protein receptors present on cell host surface. Spike is a homotrimer that emerges from the virion, each monomer containing two subunits named S1 and S2, which are related to cell recognition and membrane fusion, respectively. S1 is subdivided in domains S1A (or NTD) and S1B (or RBD), with experimental and in silico studies suggesting that the former binds to sialic acid-containing glycoproteins, such as CD147, whereas the latter binds to ACE2 receptor. Recent findings indicate that the ABO blood system modulates susceptibility and progression of infection, with type-A individuals being more susceptible to infection and/or manifestation of a severe condition. Seeking to understand the molecular mechanisms underlying this susceptibility, we carried out an extensive bibliographic survey on the subject. Based on this survey, we hypothesize that the correlation between the ABO blood system and susceptibility to SARS-CoV-2 infection can be presumably explained by the modulation of sialic acid-containing receptors distribution on host cell surface induced by ABO antigens through carbohydrate-carbohydrate interactions, which could maximize or minimize the virus Spike protein binding to the host cell. This model could explain previous sparse observations on the molecular mechanism of infection and can direct future research to better understand of COVID-19 pathophysiology.

Comparison of behavioral, neuroprotective, and proinflammatory cytokine modulating effects exercised by (+)-cis-EC and (-)-cis-EC stereoisomers in a PTZ-induced kindling test in mice.

Epoxy-carvone (EC) has chiral centers that allow generation of stereoisomers, including (+)-cis-EC and (-)-cis-EC, whose effects in the kindling tests have never been studied. Accordingly, this study aims to comparatively investigate the effect of stereoisomers (+)-cis-epoxy-carvone and (-)-cis-epoxy-carvone on behavioral changes measured in scores, in the levels of cytokines (IL-1ß, IL-6, and TNFα) and neuronal protection in the face of continuous treatment with pentylenetetrazol. Swiss mice were divided into five groups (n = 10), receiving vehicle, (+) - cis-EC, (-) - cis-EC (both at the dose of 30 mg/kg), and diazepam (4 mg/kg). Thirty minutes after the respective treatment was administered to the animals one subconvulsive dose of PTZ (35 mg/kg). Seven subconvulsives treatments were made on alternate days, in which each treatment several parameters were recorded. In the eighth treatment, the animals receiving the highest dose of PTZ (75 mg/kg) and were sacrificed for quantification of cytokines and histopathologic analysis. All drugs were administered by intraperitoneal route. In the kindling test, (+)-cis-EC and (-)-cis-EC reduced the average scores. The stereoisomer (+)-cis-EC decreased levels of proinflammatory cytokines IL-1ß, IL-6, and TNFα, whereas comparatively (-)-cis-EC did not reduce IL-1ß levels. Histopathological analysis of the mice hippocampi undergoing this methodology showed neural protection for treated with (+)-cis-EC. The results suggest that the anticonvulsant effect of (+)-cis-EC possibly takes place due to reduction of proinflammatory cytokines involved in the epileptogenic process, besides neuronal protection, yet further investigation of the mechanisms involved is required.

Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population.

Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraíba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific - PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.

Anticonvulsive activity of (1S)-(-)-verbenone involving RNA expression of BDNF, COX-2, and c-fos.

(1S)-(-)-verbenone (VRB) is a monoterpene present in the essential oils of many plants which has shown therapeutic effect; however, its anticonvulsant activity has not yet been evaluated. The present work sought to investigate the anticonvulsant activity of VRB using pilocarpine and pentylenetetrazole-induced seizure testing; seeking also probable mechanisms of action. VRB caused no significant changes in motor coordination. Also, no significant data was observed in the pilocarpine-induced seizure tests. In the PTZ-induced seizures test, VRB showed anticonvulsant activity at doses of 200 mg/kg i.p. (733 ± 109.4 s) and 250 mg/kg i.p. (648.8 ± 124.5 s) significantly increasing the latency to onset of first seizure as compared with the vehicle group (51.8 ± 2.84 s). Pretreatment with flumazenil (FLU) did not reverse the anticonvulsive effect of VRB; however, it was able to upregulate BDNF and COX-2 genes and downregulate c-fos. The findings suggest that the anticonvulsant effects of VRB may be related to RNA expression modulations of COX-2, BDNF, and c-fos.

Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers.

Stereoisomers of the monoterpene epoxycarvone (EC), namely (+)-cis-EC, (-)-cis-EC, (+)-trans-EC, and (-)-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ)-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg) increased the latency to seizure onset, and afforded 100% protection against the death of the animals. In the maximal electroshock-induced seizures (MES) test, prevention of tonic seizures was also verified for all of the isomers tested. However, the isomeric forms (+) and (-)-trans-EC showed 25% and 12.5% inhibition of convulsions, respectively. In the pilocarpine-induced seizures test, all stereoisomers demonstrated an anticonvulsant profile, yet the stereoisomers (+) and (-)-trans-EC (at 300 mg/kg) showed a more pronounced effect. A strychnine-induced anticonvulsant test was performed, and none of the stereoisomers significantly increased the latency to onset of convulsions; the stereoisomers probably do not act in this pathway. However, the stereoisomers (+)-cis-EC and (+)-trans-EC greatly increased the latency to death of the animals, thus presenting some protection. The four EC stereoisomers show promise for anticonvulsant activity, an effect emphasized in the isomers (+)-cis-EC, (+)-trans-EC, and (-)-trans-EC for certain parameters of the tested methodologies. These results serve as support for further research and development of antiepileptic drugs from monoterpenes.

Dideoxy single allele-specific PCR - DSASP new method to discrimination allelic

Gastric cancer (GC) is a multifactorial disease with a high mortality rate in Brazil and worldwide. This work aimed to evaluate single nucleotide polymorphisms (SNP) rs1695, in the Glutathione S-Transferase Pi (GSTP1) gene in GC samples by comparative analysis Specific PCR - ASP and Dideoxy Single Allele-Specific PCR - DSASP methods. The DSASP is the proposed new method for allelic discrimination. This work analyzed 60 GC samples, 26 diffuse and 34 intestinal types. The SNP rs1695 of the GSTP1 gene was significantly associated with GC analyzed by DSASP method (χ2 = 9.7, P < 0.05). A comparative analysis of the data obtained from both methods did not differ significantly (χ2 = 0.08, P > 0.05). These results suggest that the SNP rs1695 of the GSTP1 gene was a risk factor associated with gastric carcinogens is and the DSASP method was a new successfully low-cost strategy to study allelic discrimination.