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Glutathione S-transferases (GSTs) detoxify toxic molecules by conjugation with reduced glutathione and regulate cell signaling. Single nucleotide polymorphisms (SNPs) of GST genes have been suggested to affect GST functions and thus to increase the risk of human hepatocellular carcinoma (HCC). As GSTA1 is expressed in hepatocytes and the rs3957357C>T (TT) SNP is known to downregulate GSTA1 mRNA expression, the aims of this study were: (i) to explore the relationship between the TT SNP in GSTA1 and the occurrence of HCC; (ii) to measure GSTA1 mRNA expression in HCCs. For that purpose, we genotyped non-tumor-tissue-derived DNA from 48 HCC patients and white-blood-cell-derived DNA from 37 healthy individuals by restriction fragment length polymorphism (RFLP). In addition, expression of GSTA1 mRNA was assessed by real-time PCR in 18 matching pairs of HCCs and non-tumor livers. Survival analysis was performed on an annotated microarray dataset containing 247 HCC patients (GSE14520). The GSTA1 TT genotype was more frequent in HCC than in non-HCC patients (27% versus 5%, respectively), suggesting that individuals carrying this genotype could be associated with 2-fold higher risk of developing HCCs (odds ratio = 2.1; p = 0.02). Also, we found that GSTA1 mRNA expression was lower in HCCs than in non-tumor livers. HCCs expressing the highest GSTA1 mRNA levels were the smallest in size (R = -0.67; p = 0.007), expressed the highest levels of liver-enriched genes such as ALB (albumin, R = -0.67; p = 0.007) and COL18A1 (procollagen type XVIII, R = -0.50; p = 0.03) and showed the most favorable disease-free (OR = 0.54; p<0.001) and overall (OR = 0.56; p = 0.006) outcomes. Moreover, GSTA1 was found within a 263-gene network involved in well-differentiated hepatocyte functions. In conclusion, HCCs are characterized by two GSTA1 features: the TT SNP and reduced GSTA1 gene expression in a context of hepatocyte de-differentiation.

The purpose of this study was to expand the mutation spectrum by searching the causative mutations in nine Lebanese families with Usher syndrome (USH) using whole-exome sequencing. The pathogenicity of candidate mutations was first evaluated according to their frequency, conservation, and in silico prediction tools. Then, it was confirmed via Sanger sequencing, followed by segregation analysis. Finally, a meta-analysis was conducted to calculate the prevalence of USH genes in the Lebanese population. Three missense mutations, two splice site mutations, and one insertion/deletion were detected in eight of the families. Four of these variants were novel: c.5535C &gt; A; p.(Asn1845Lys) in exon 41 of CDH23, c.7130G &gt; A; p.(Arg2377Gln) in exon 32 of ADGRV1, c.11390-1G &gt; A in USH2A, and c.3999–6A &gt; G in PCDH15. All the identified mutations were shown to be likely disease-causing through our bioinformatics analysis and co-segregated with the USH phenotype. The mutations were classified according to the ACMG standards. Finally, our meta-analysis showed that the mutations in ADGRV1, USH2A, and CLRN1 are the most prevalent and responsible for approximately 75% of USH cases in Lebanon. Of note, the frequency USH type 3 showed a relatively high incidence (23%) compared to the worldwide prevalence, which is around 2–4%. In conclusion, our study has broadened the mutational spectrum of USH and showed a high heterogeneity of this disease in the Lebanese population.

The population exposure to pesticides is dramatically increasing in the last few decades because of the widespread uncontrolled use of pesticides especially in the developing countries. In our study, we examine the effect of 6 mg/kg of Captan, a fungicide, mixed with diet, on body weight, muscle mass, proteins content and contractile response of slow‐twitch skeletal muscles (soleus). As compared with controls placebo animals, 2 weeks of treatment induces a significant increasing in body weight (15%) and muscle mass (14%) which could be due in part to the increasing in soluble and Myofibrillar proteins content. Moreover, our results show that Captan treatment induces a decreasing by 15% in the expression of MHC I isoforms (Control: 88.7 ± 3.2 ; Captan: 75.3 ± 2.3) and an increasing in the expression of MHCII isoforms (Control: MHC IIa: 1.09 ±0.61; MHC IIb: 10.34±2.33; MHC IIx/d: 1.28±1.02; Captan: MHC IIa: 9.79±1.61; MHC IIb: 17.91±1.40; MHC IIx/d: 12.28±1.72; p<0.05; n= 10). Thus, this study shows that treatment by Captan mixed with diet can induce an effect in myofibrillar proteins of slow‐ twitch mammalian skeletal muscles by shifting in the expression of slow MHC type into fast MHC type.

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