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Agostinelli, E.

Publications and source records attributed to Agostinelli, E..

2 recordsLinked to original sources

Bronchial epithelial IB3-1 cells exposed to the anti-SARS-CoV2 BNT162b2 vaccine: induction of apoptosis is partially reversed by Aged Garlic Extract (AGE) and its bioactive components S-allyl-Cysteine and S1-propenyl-l-Cysteine

The Spike protein (S-protein) of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) exhibits important and negative effects on human cells. Accordingly, the adverse effects of COVID-19 mRNA vaccines could be due to the presence of circulating spike and need to be mitigated. One of the biological activities of the Spike protein (and, indirectly, of the Spike-producing vaccines) is the high induction of apoptosis and pro-inflammatory gene expression in different cellular systems. We have recently demonstrated that Aged Garlic Extract (AGE) and its components S-allyl-Cysteine (SAC) and S1-propenyl-I-Cysteine (S1PC) are potent inhibitors of the expression of pro-inflammatory genes induced by treatment of the bronchial epithelial IB3-1 cells with the Spike RNA-based BNT162b2 vaccine. The main purpose of the present study was to determine (a) whether treatment of the IB3-1 bronchial epithelia cells with the BNT162b2 vaccine is associated with activation of the apoptotic pathway and (b) whether AGE, SAC and S1PC have any effect of therapeutic relevance on this experimental model system. We have exposed IB3-1 cells to increasing amounts of the BNT162b2 vaccine and, after 3 days of culture, apoptosis was assessed using the Annex V and the Caspase 3/7 apoptosis assays. The results obtained demonstrated highly significant increase of the percentage of apoptotic cells after treatment of IB3-1 cells with the BNT162b2 vaccine. The percentage of apoptotic cells was found to be significantly reduced in cell populations treated with the BNT162b2 vaccine in the presence of AGE, SAC and S1PC. The main conclusion of the results of our study is that Aged Garlic Extracts, and its components S-allyl-Cysteine and S1-propenyl-l-Cysteine are able to mitigate the pro-apoptotic effects of the Spike-producing BNT162b2 vaccine using the bronchial epithelial IB3-1 cell line as experimental model system. The efficacy of the reversion of BNT162b2 induced apoptosis suggests that AGE, SAC and S1PC should be considered for the development of protocols aimed at counteracting apoptosis induced by the Spike mRNA-based COVID-19 vaccines. This might be of potential clinical relevance, since one of the biological adverse effects of Spike protein (and, indirectly, of the Spike-producing vaccines) is the high induction of apoptosis in different cellular systems.

cell biology↗

Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function

Microsatellite expansions of CCTG repeats in the CNBP gene leads to accumulation of toxic RNA and have been associated to DM2. However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-type zinc finger RNA binding protein that regulates translation and is required for mammalian development. Here we show that depletion of Drosophila CNBP in muscles causes age-dependent locomotor defects that are correlated with impaired polyamine metabolism. We demonstrate that the levels of ornithine decarboxylase (ODC) and polyamines are significantly reduced upon dCNBP depletion. Of note, we show a reduction of the CNBP-polyamine axis in muscle from DM2 patients. Mechanistically, we provide evidence that dCNBP controls polyamine metabolism through binding dOdc mRNA and regulating its translation. Remarkably, the locomotor defect of dCNBP-deficient flies is rescued by either polyamine supplementation or dOdc1 overexpression. We suggest that this dCNBP function is evolutionarily conserved in vertebrates with relevant implications for CNBP-related pathophysiological conditions. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC="FIGDIR/small/441910v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@a8c31corg.highwire.dtl.DTLVardef@1a18260org.highwire.dtl.DTLVardef@76a3d4org.highwire.dtl.DTLVardef@fdd041_HPS_FORMAT_FIGEXP M_FIG C_FIG CNBP controls muscle function by regulating the polyamine metabolism O_LILack of dCNBP impairs locomotor function through ODC-polyamine downregulation C_LIO_LIdCNBP binds dOdc mRNA and regulates its translation C_LIO_LIPolyamine supplementation or dOdc1 reconstitution rescues locomotor defects C_LIO_LICNBP-ODC-polyamine levels are reduced in muscle of DM2 patients C_LI

genetics↗