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Δευτέρα 16 Μαΐου 2022

ORF8 protein of SARS‐CoV‐2 reduces male fertility in mice

alexandrossfakianakis shared this article with you from Inoreader

Abstract

As one of the most rapidly evolving proteins of the genus Betacoronavirus, ORF8's function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by ROS scavenger and ER-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion,we examined the plasma samples of COVID-19 convalescent patients and found that the patients aged 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail-vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle- and ORF8-treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in five-week-old male mice. Furthermore, the analysis of gene expression in the testes between vehicle- and ORF8-treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of SARS-CoV-2 infection on the human reproductive system.

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In silico analysis of mutations near S1/S2 cleavage site in SARS‐CoV‐2 spike protein reveals increased propensity of glycosylation in Omicron strain

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Abstract

Cleavage of the Severe Respiratory Syndrome Coronavirus–2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. Mutations near cleavage motifs, such as the S1/S2 and S2' sites, may alter interactions with host proteases and, thus, the potential for fusion. The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins has not yet been explored. Using sequence and structure-based bioinformatics, mutations near the VOC/VOI spike protein cleavage sites were inspected for their structural effects. All mutations found at the S1/S2 sites were predicted to increase affinity to the furin protease but not TMPRSS2. Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directe d kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. Further experimental work is needed to confirm the effect of mutations and post-translational modifications on SARS-CoV-2 spike protein cleavage sites.

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Radiographic bone volume alteration after jaw cyst enucleation with or without simultaneous bone grafts: A prospective randomized study

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Objective

This study was aimed to evaluate bone healing after jaw cyst enucleation with or without bone substitutes by cone beam computed tomography, and to analyze potential influence factors for bone formation as well.

Materials and Methods

Sixty seven jaw cyst patients were randomly assigned to two groups. Thirty three patients in control group accepted cystectomy without any filling material. The rest 34 bone cavities which filled with xenograft (DBBM, Bio-Oss®) and covered by absorbable membrane (Bio-Gide®) were included in the guided bone regeneration (GBR) group. All patients were examined with cone bean computerized tomography before operation, 3 and 6 months after surgery. Linear regression analysis was applied to evaluate the influence factors of bone healing.

Results

There was no significant difference in bone formation rate at 3 months after enucleation, with shrinkage rate (SR) of cystic lesion in control group and GBR group of 26.43 ± 14.98% and 20.78 ± 10.80%, respectively (p > 0.05). Larger shrinkage area in GBR group was detected on postoperative radiographs after 6 months with SR of 60.11 ± 19.23%, when compared to those in patients without filling (6 months SR: 48.63 ± 19.39%, p = 0.018, <0.05). Linear regression analysis showed that cyst size was negatively correlated with bone formation.

Conclusion

GBR with bovine xenograft and absorbable membrane showed considerable bone regeneration property in the healing of jaw cystic defects after enucleation of radicular cysts. Cyst size showed a suppressive influence on bone formation.

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