The novel coronavirus disease 2019 (COVID-19) has led to a serious global pandemic. Although an oxidative stress imbalance occurs in COVID-19 patients, the contributions of thiol/disulphide homeostasis and nitric oxide (NO) generation to the pathogenesis of COVID-19 have been poorly identified. Therefore, the aim of this study was to evaluate the effects of antiviral drug therapy on the serum dynamics of thiol/disulphide homeostasis and NO levels in COVID-19 patients. A total of 50 adult patients with COVID-19 and 43 sex-matched healthy control subjects were enrolled in this prospective study. Venous blood samples were collected immediately on admission to the hospital within 24 h after the diagnosis (pre-treatment) and at the 15th day of drug therapy (post-treatment). Serum native thiol and total thiol levels were measured, and the amounts of dynamic disulphide bonds and related ratios were calculated. The average pre-treatment total and native thiol levels were significantly lower than the post-treatment values (P < 0.001 for all). We observed no significant changes in disulphide levels or disulphide/total thiol, disulphide/native thiol, or native thiol/total thiol ratios between pre- and post-treatments. There was also a significant increase in serum NO levels in the pre-treatment values when compared to control (P < 0.001) and post-treatment measurements (P < 0.01). Our results strongly suggest that thiol/disulphide homeostasis and nitrosative stress can contribute to the pathogenesis of COVID-19. This study was the first to show that antiviral drug therapy can prevent the depletion in serum thiol levels and decrease serum NO levels in COVID-19 patients.

Spinal musküler atrofi (SMA), survival motor neuron (SMN1) genindeki delesyonlar veya mutasyonların neden olduğu otozomal resesif bir nöromusküler bir hastalıktır. Çocuk ölümlerinin en yaygın kalıtsal nedenidir. SMN1, tüm ökaryotik organizmaların genomunda tek kopya olarak bulunur. Genomik duplikasyon ile ikinci bir gen SMN2 insanlarda ortaya çıkmıştır. Hastaların yaklaşık %95'i SMN1 geninin ekzon 7'sinde homozigot delesyonlara sahiptir. Bundan dolayı SMN proteini yeterli miktarda üretilemez. SMN2, ekzon 7'deki sübstitüsyondan (C-T) dolayı küçük miktarda fonksiyonel SMN proteini üretir. SMA; başlangıç yaşı, motor gerilemenin şiddeti ve beklenen yaşam süresine göre beş tip (0-IV) olarak sınıflandırılmaktadır. Tip I (Werding-Hoffmann) en ciddi formudur ve özellikle yenidoğanları etkilemektedir. SMA hastalarındaki fenotipik değişkenlik, SMN2 geninin kopya sayısı ile ilişkilidir. SMN2'nin kopya sayısı hastalığın şiddeti ile korelasyon göstermektedir. SMN proteini, nöronal hücrelerde mRNA transportu, RNA metabolizması gibi anahtar düzenleyici rollere sahiptir. Günümüzde SMA tedavisi için ana hedef; küçük moleküller, oligonükleotidler ve gen replasmanı ile motor nöronlarda SMN seviyesini artırmaktır. SMA tedavisi için kök hücre çalışmaları da yapılmaktadır. FDA, 2016 yılından beri SMA tedavisi için üç yeni ilaç onayladı. Bu ilaçlar; nusinersen (oligonükleotit), onasemnogene abeparvovecxioi (gen replasmanı) ve risdiplam (SMN2 gen modülatörü)'dır. İlaçların etkililiğinde erken tanı önemli bir role sahiptir. SMN bağımlı terapötik yaklaşımlar presemptomatik olarak uygulandığında motor nöron disfonksiyonları reversible olabilir.

Oxidative stress may contribute to the pathogenesis of congenital heart defects, but the role of dynamic thiol/disulphide homeostasis has not been evaluated. The objective of this study was to assess whether there are changes in thiol/disulphide homeostasis and nitric oxide levels in children with tetralogy of Fallot (TOF) and ventricular septal defect (VSD). A total of 47 children with congenital heart defects (24 TOF and 23 VSD) and 47 healthy age- and sex-matched controls were included in this study. Serum total thiol and native thiol levels were measured using a novel automatic spectrophotometric method. The amount of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide levels were detected using a chemiluminescence assay. We found that the average native thiol, total thiol, and disulphide levels were decreased in patients with VSD when compared with healthy individuals (p < 0.001, p < 0.001, and p < 0.01, respectively). While native thiol levels were decreased (p < 0.01), disulphide levels were elevated in the TOF group (p < 0.05). We observed marked augmentation of disulphide/native thiol (p < 0.001) and disulphide/total thiol ratios (p < 0.01) in the TOF group. However, there was a significant decrease in native thiol/total thiol ratio in patients with TOF. No significant changes in these ratios were noted in the VSD group. We detected significant elevations in serum nitric oxide levels in children with TOF and VSD (p < 0.001 for all). These results are the first to demonstrate that thiol/disulphide homeostasis and nitric oxide are associated with TOF and VSD in children.

Background Alteration in thiol level under oxidative stress may contribute to community‐acquired pneumonia (CAP). The goal of this study was to determine whether there are changes in thiol/disulfide homeostasis and nitric oxide (NO) in children with CAP. Methods In total, 130 participants were involved in the study. Of these, 65 had been diagnosed with CAP on admission, and the remaining 65 were healthy individuals. Serum total thiol and native thiol were measured in each participant using a novel automated spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. Serum NO was measured on chemiluminescence assay. Results Average native thiol, total thiol, and disulfide in the CAP group were significantly lower than in the healthy individuals (P < 0.0001, P < 0.0001, P = 0.0126, respectively). In addition, disulfide/native thiol (P = 0.0002), and disulfide/total thiol ratios (P = 0.0004) were significantly higher, whereas the native thiol/total thiol ratio (P = 0.0004) was lower in the CAP group. High serum NO was noted in the CAP group (P = 0.0003), but there was no marked correlation between thiol/disulfide and NO. Conclusion The changes in endogenous thiol levels under oxidative stress may be associated with the pathogenesis of CAP in pediatric patients.

The annual economic burden of visual disorders in the United States was estimated as $139 billion. The World Health Organization has listed glaucoma in the top 10 priority eye diseases. Primary open-angle glaucoma (POAG) is a common subtype, with a lack of clinical tools for early diagnosis. The Rho GTPases belong to the Ras superfamily of proteins; the RhoA immunostaining in the optic nerve head in human glaucoma is reportedly increased. We investigated the association of polymorphisms in the Ras Homolog Family Member A, B, C, and D genes (RHOA, RHOB, RHOC, and RHOD, respectively). In a total sample of 361 unrelated subjects (179 patients with POAG and 182 age- and sex-matched healthy controls), RHOA (rs6784820, rs974495), RHOB (rs62121967), RHOC (rs11102522), and RHOD (rs61891303, rs2282502) polymorphisms were characterized by the BioMark HD dynamic array system with real-time polymerarse chain reaction. Among these candidate genetic markers and considering the Bonferroni correction, RHOA rs974495 polymorphism was significantly associated with POAG (p = 0.0011), with the TT genotype increasing the disease risk 4.9 times (95% CI 1.630-15.023). The allele and haplotype distributions of the above RHO candidate polymorphisms did not diplay a significant association. This is the first study, to the best of our knowledge, to identify a significant genotypic association between POAG and RHOA gene rs974495 polymorphism. These observations warrant replication in independent samples in the pursuit of precision medicine for rapid and early glaucoma diagnosis, and molecular targets for innovation in therapeutics of this common eye disease.