Attenuation of Oxidative Stress and Cytokines in Rabbits with Experimentally Induced Hyperthyroidism by Ethanolic Red Cabbage Extract

The protective effects of red cabbage extract (RCE) on oxidative damage in rabbits with experimentally induced hyperthyroidism were studied on forty male New Zealand rabbits. The experimental animals were randomly divided into 4 groups :(healthy as (control), hyperthyroidism, hyperthyroidism treated with vitamine E and hyperthyroidism treated with RCE .Hyperthyroidism was induced by oral administration of 20 μg/kg b.w/day L-thyroxine for 4 weeks. At the end of the experimental period, blood samples were taken from heart puncture of all animals for the determination of oxidant/antioxidant biomarkers: lipid peroxidation marker malonaldehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), Catalase (CAT) and superoxide dismutase (SOD) ,triiodothyronine (T3), thyroxine (T4) , thyroxine-stimulating hormone (TSH),interleukin 6 (IL-6),interleukin 10 (IL-10) and tumor necrosis factor alpha(TNF-α) levels. Our results indicate that levels of MDA, T3 , T4 ,IL-6, IL-10 and TNF-α were significantly increased(P<0.05) in sera of the hyperthyroid animal group, while SOD; GPx, CAT, GSH and TSH levels were decreased significantly (p<0.05) compared to the control group. Hyperthyroid rabbits treated with 100 mg/kg.b.w daily of RCE for 4 weeks decreased significantly the elevated MDA, T3 ,T4, IL-6, IL-10 and TNF-α levels and restore levels of GSH, GPx, SOD, CAT and TSH to control value. In conclusion, results indicated that RCE was beneficial as a protective agent against oxidative stress induced by hyperthyroidism and it had antihyperthyroid activity for the first time

Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome

Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.</p

Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate

The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome