Potential antiviral effects of pantethine against SARS-CoV-2.

SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection, in Vero E6 cells and in Calu-3a cells. Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome.

Identification by whole-exome sequencing of new single-nucleotide polymorphisms associated with molar-incisor hypomineralisation among the Lebanese population.

OBJECTIVE: Molar-incisor hypomineralization (MIH) is a developmental qualitative enamel defect, causing a worldwide challenging dental problem. The etiology of this defect remains unclear. Here we identify by whole-exome sequencing (WES) new single-nucleotide polymorphisms (SNPs) in genes expressed during enamel mineralization and in those modulating prenatal, natal and postnatal risk factors among the Lebanese MIH children: immune system and xenobiotic detoxification. DESIGN: Dental examination for MIH was performed based on the MIH index for diagnostic criteria. Saliva samples were collected from 37 non-related, MIH-diagnosed subjects for DNA extraction. WES was performed on the Illumina HiSeq2000 platform. The χ2 test and Fisher's exact test were used to determine relationship between SNPs frequencies and MIH. OR and its 95% CI were used to report the strength of association. The significance threshold was set at 0.05. RESULTS: Among the Lebanese population, 37 SNPs presented a significant association with MIH in the following genes: AMTN, MMP-20, STIM1, STIM2, ORAI1, SLC34A2, SLC34A3, VDR, PVALB, HSP90B1, TRPM7, SLC24A4, CA6, SLC4A2, TNFRSF11A, IL10RB, ARNT, ESR1 and CYP1B1. CONCLUSION: This is the first WES study conducted in patients with MIH. Yet, interactions between polymorphisms in different gene categories are to be investigated for a better assessment of MIH susceptibility.

Relation between molar-incisor hypomineralization (MIH) occurrence and war pollutants in bombarded regions: Epidemiological pilot study in Lebanon.

BACKGROUND: Molar-incisor hypomineralization (MIH), a developmental enamel defect affecting one or more first permanent molars (FPMs) and sometimes incisors (PIs), is one of the most common pandemic health problems in the world. MIH etiology is still unclear and has been suggested to be related to exposure to environmental toxicants during enamel mineralization. AIMS: To assess the susceptibility to MIH occurrence in regards to war pollutants through the investigation of the prevalence and the clinical characteristics of MIH in a group of Lebanese children whose FPMs and PIs enamel mineralization coincides with the 2006 Lebanese war. PATIENTS AND METHODS: This cross-sectional study was performed in schools from different regions of Lebanon. Schoolchildren born in 2004, 2005, 2006, and 2007 were examined for MIH. Clinical status, lesion type, extension, and severity were recorded using the short form chart of the MIH index. Pearson's Chi-square or Fischer's exact test were used to determine if there is a significant relationship between categorical variables. RESULTS: An overall MIH prevalence of 22.93% has been reported. Forty-seven point seventy-five per cent had both molars and incisors affected. Demarcated opacities were the most frequently observed clinical status. Most of the MIH FPMs and PIs were mildly affected with lesions extended on less than the third of the tooth surface. CONCLUSIONS: MIH prevalence among children born around 2006 Lebanese war is high. The hypothesis of a relation between MIH susceptibility and war pollutants in bombarded regions is legible but requires to be elucidated via additional in vitro and in vivo studies for accurate risk assessment.

Molar-incisor hypomineralisation in Lebanon: association with prenatal, natal and postnatal factors.

BACKGROUND: Molar-incisor hypomineralisation is an enamel developmental defect highly prevalent in Lebanon. Literature suggests that perinatal conditions and childhood illnesses might be potential aetiological factors for this affection. AIMS: This case-control study aimed to investigate the association of MIH with prenatal, natal and postnatal factors amongst 7-9 years Lebanese children and to end up with recommendations to overcome its occurrence. METHODS: Self-administered, structured questionnaire including potential etiological factors was distributed to 659 MIH and non-MIH children's parents. The analysis of data was carried out using Statistical Package for Social Sciences Computer Software (SPSS 21.0, Inc., Chicago, IL, USA). For Statistical analysis, Pearson's chi-square, Fischer's exact test and multivariate regression model were used. A p value of less than 0.05 was considered statistically significant. RESULTS: Children whose mothers had consumed food and drinks canned during pregnancy had 2.9 (CI: 1.367 to 6.187) times more likely to have MIH. Those who had history of taking antibiotics had 2.15 (CI: 1.186 to 3.909) times higher odds of MIH than those who did not have while those who had fever episodes during the early childhood years were 2.057 (CI: 1.149 to 3.683) times more likely to develop MIH. CONCLUSION: During early childhood, careful handling of high fever, greater public awareness regarding misuse of antibiotics and education about bisphenol A and how to avoid it during pregnancy and breastfeeding are recommended to decrease the occurrence of MIH.

Molar incisor hypomineralisation in Lebanon: prevalence and clinical characteristics.

BACKGROUND: Molar incisor hypomineralisation (MIH) is a qualitative enamel developmental defect affecting 1-4 first permanent molars and sometimes the permanent incisors. MIH is extremely widespread around the world and presents a considerable clinical problem in paediatric dentistry. Although, little prevalence data exist for Middle East populations including the Lebanese one. AIM: The objectives of this study were to investigate the prevalence of MIH in 7-9-year-old Lebanese children, with relevance to gender, jaw and side distribution, and to assess the clinical status, extent and severity of MIH lesions of the affected teeth. DESIGN: Representative sample (n = 659) of 7-9-year-old Lebanese children attending private and public schools distributed throughout Lebanon was examined for MIH. Clinical status, extent and severity of MIH lesions on FPMs and permanent incisors were scored using the short-form grading method (MIH index) of Ghanim et al. (Eur Arch Paediatr Dent 16:235-246, 2015). RESULTS: An overall MIH prevalence of 26.7% was reported with no significant predilection for girls over boys. 52.8% of the cases present with only molars and. 47.2% with both molars and incisors and did not present any significant difference between upper and lower jaws (P = 0.325). Left-side FPMs were more affected than the right ones (P = 0.0218). Central incisors were significantly more affected than the laterals in both jaws (P < 0.0001). Maxillary central incisors were significantly more affected than their mandibular counterparts (P < 0.0001). Most of the clinical status was demarcated opacities extended on less than the third of the tooth surface. The extent of lesions correlated significantly with the number of affected molars. Most of the affected teeth presented with mild defects and the degree of severity was not correlated with gender but significantly increased with age. CONCLUSIONS: MIH is prevalent in Lebanon. Further studies are required to analyse the possible systemic and environmental etiologies among Lebanese children.

Requirement for Daxx in mature T-cell proliferation and activation.

The protein Daxx promotes Fas-mediated cell death through activation of apoptosis signal-regulating kinase 1, leading to the activation of the MAPKs JNK and p38. Owing to the in utero lethality of daxx-deficient mice, the in vivo role of Daxx has been so far difficult to analyze. We have generated transgenic mice expressing a dominant-negative form of Daxx (Daxx-DN) in the T-cell lineage. We show that Daxx is recruited to the Fas receptor upon FasL engagement and that Daxx-DN expression protects activated T cells from Fas-induced cell death, by preventing the death-inducing signal complex to be properly formed. Normal lymphocyte development and homeostasis are nevertheless observed. Interestingly, we report that both in vitro and in vivo stimulation of Daxx-DN T-lymphocytes leads to increased proliferative T-cell responses. This increased proliferation is associated with a marked increase in tyrosine phosphorylation of LAT and ZAP70 as Daxx-DN favor their recruitment to the T-cell receptor (TCR) complex. These findings identify Daxx as a critical regulator of T-lymphocyte homeostasis by decreasing TCR-induced cell proliferation and by promoting Fas-mediated cell death.