Autosomal recessive corneal hereditary endothelial dystrophy (CHED) is a rare congenital disorder of cornea. Mutations in SLC4A11 gene are associated with CHED phenotype. CHED is also an early feature of Harboyan syndrome. The aim of the present study was to identify genetic mutations in the SLC4A11 gene in CHED cases belonging to inbred Pakistani families. Furthermore, all homozygous mutation carriers were investigated for hearing deficit.
Methods and results
This study included consanguineous CHED families presented at Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan from June 2018 to September 2018. DNA was extracted from blood samples. Direct sequencing of SLC4A11 gene was performed. All identified variants were evaluated by in silico programs i.e., SIFT, PolyPhen‐2, and MutationTaster. Pathogenicity of the two identified splice site variants was analyzed by Human Splicing Finder and MaxEnt Scan. Screening of five CHED families revealed a total of three previously un reported (p.Arg128Gly, c.2241-2A?>?T and c.1898-2A?>?C in family CHED19, CHED22 and CHED26 respectively) and two already reported homozygous disease causing variants (p.Arg869Cys and p.Val824Met in family CHED24 and CHED25 respectively) as predicted by mutation taster. All of these variants segregated with disease phenotype and were not detected in controls.
Conclusion
Affected individuals of the five CHED families screened in this study had the disease due to SLC4A11 mutations and progressing to Harboyan syndrome. Identification of previously unreported mutations aid to heterogeneity of SLC4A11 and CHED pathogenesis as well as helped to provide genetic counseling to affected families.
Testosterone and ten of its metabolites were examined as inhibitors of butyrylcholinesterase. A significant enzyme inhibition activity (IC50 = 1.55 μM) was observed for androst-4-en-3,7-dione. The kinetic parameters of butyrylcholinesterase inhibition were determined and molecular docking was carried out in order to develop a better understanding of the inhibitor-enzyme interactions. The results showed that the inhibition was non-competitive, stabilized mainly by hydrogen bonds and hydrophobic interactions between the inhibitor and butyrylcholinesterase. 相似文献
An efficient one-pot three-component synthesis of thiadiazole N-nucleosides with high atom economy from β-D-ribosylhydrazine, aryl thiamide, and aromatic aldehyde promoted by (diacetoxyiodo)benzene under microwave irradiation is reported. The strategy involves formation of thiourea derivatives by microwave-assisted addition of an arylisothiocyanate formed in situ by (diacetoxyiodo)benzene-promoted oxidative rearrangement of an aryl thiamide with Schiff bases of β-D-ribosylhydrazine and a substituted/unsubstituted aromatic aldehyde. The thiourea intermediate on intramolecular heterocyclization yielded thiadiazole N-nucleosides, 2-(arylimino)-3-(β-D-ribosyl)-5-aryl-1,3,4-thiadiazoles. The whole reaction sequence proceeded with quantitative transformation of reactants into thiadiazole N-nucleosides at an ambient temperature. The reaction sequence is supported by isolation of Schiff bases and their quantitative conversion into final product by reaction with arylisothiocyanate under the same reaction conditions. 相似文献
Mutations in SLC26A4 cause either syndromic or nonsyndromic hearing loss. We identified a link between hearing loss and DFNB4 in 3 of the 50 families participating in this study. Sequencing analysis revealed two SLC26A4 mutations, p.V239D and p.S57X, in affected members of the 3 families. These mutations have been previously reported in deaf individuals from the subcontinent, all of whom manifested profound deafness. The patients investigated in our study exhibited moderate to severe hearing loss. Our results show that inactivating SLC26A4 mutations that cause profound deafness can also be involved in the etiology of moderate to severe hearing loss. The type of mutation cannot predict the severity of the hearing loss in all cases, and there may be additional epistatic interactions that could modify the phenotype. 相似文献
Recent studies have reported oxidative damage due to bisphosphonate (BP) in various cancer tissues and neurons, although basic fibroblast growth factor (bFGF) induced antioxidant effects in the cells. The bFGF may modulate the BP-induced oxidative stress in oral epithelium of rats. This study was undertaken to explore possible beneficial antioxidant effects of bFGF on oxidative stress induced by BP in oral epithelium of rats. Twenty-eight rats were equally divided into four groups. The first group was used as control. The second, third and fourth groups intraperitoneally received BP (zoledronic acid), bFGF and BP + bFGF. At the end of 10 weeks, the rats were sacrificed, and oral epithelium samples were taken for analyses. In BP group, the lipid peroxidation levels were increased in the oral epithelium, while the activities of glutathione peroxidase (GSH-Px) and the concentrations of total antioxidant status (TAS) were decreased. In rats treated with bFGF, lipid peroxidation levels decreased, and the activities of GSH-Px and concentrations of TAS improved in the oral epithelium. However, zinc and copper levels were decreased in the oral epithelium by BP and bFGF treatments. Concentrations of vitamin E and reduced glutathione in the samples did not change in the groups. In conclusion, treatment with bFGF modulated the antioxidant redox system and reduced the oral epithelium oxidative stress induced by BP. However, zinc and copper levels were decreased by BP and bFGF treatments. 相似文献
Current reports on trace elements, oxidative stress, and the effect of antiepileptic drugs are poor and controversial. We aimed to review effects of most common used antiepileptics on antioxidant, trace element, calcium ion (Ca2+) influx, and oxidant systems in human and experimental animal models. Observations of lower blood or tissue antioxidant levels in epileptic patients and animals compared to controls in recent publications may commonly support the proposed crucial role of antioxidants in the pathogenesis of epilepsy. Effects of old and new antiepileptics on reactive oxygen species (ROS) production in epilepsy are controversial. The old antiepileptic drugs like valproic acid, phenytoin, and carbamazepine induced ROS overproduction, while new epileptic drugs (e.g., topiramate and zonisamide) induced scavenger effects on over production of ROS in human and animals. Antioxidant trace element levels such as selenium, copper, and zinc were generally low in the blood of epileptic patients, indicating trace element deficiencies in the pathogenesis of epilepsy. Recent papers indicate that selenium with/without topiramate administration in human and animals decreased seizure levels, although antioxidant values were increased. Recent studies also reported that sustained depolarization of mitochondrial membranes, enhanced ROS production and Ca2+ influx may be modulated by topiramate. In conclusion, there is a large number of recent studies about the role of antioxidants or neuroprotectants in clinical and experimental models of epilepsy. New antiepileptic drugs are more prone to restore antioxidant redox systems in brain and neurons. 相似文献
Populations of three salt tolerant forage grasses (Cynodon dactylon, Imperata cylindrica, and Sporobolus arabicus) were collected from the salt-affected soils of the Salt Range and normal non-saline soils of the Faisalabad region to assess
their mechanism of adaptation to saline stress by determining ion relations and some specific anatomical modifications. The
population of S. arabicus from the Salt Range showed increased growth (root and shoot length, and root and shoot dry weights) under saline conditions.
Salt tolerance in this species was related to structural modifications such as increased area of root, stem, leaf blade, and
leaf sheath for toxic ion accumulation, increased vesicular hair density in leaves and aerenchyma formation in leaf sheath
for ion exclusion. Uptake of toxic ions was high in the Salt Range population of C. dactylon and salt tolerance was related to ion exclusion through specific leaf structural modifications such as vesicular hairs. Salt
tolerance in the Salt Range population of I. cylindrica was mainly associated with restricted uptake of toxic Na+ and Cl− at root level, and accumulation of toxic ions via increased succulence in leaf blades and leaf sheaths in addition to some
excretion of toxic ions through leaf sheath aerenchyma. 相似文献
Behçet disease (BD) is a chronic, inflammatory, and multisystemic condition with an uncertain pathogenesis. One of the major immunologic findings in BD pathogenesis is increase in activity of neutrophil. An increase in the cytosolic free Ca2+ [Ca2+]i concentration that induces Ca2+ signaling is an important step that participates in the neutrophil activation and reactive oxygen species production that leads to tissue damage in body cells. We aimed to investigate the effects of colchicine on oxidative stress and Ca2+ release in serum and neutrophil of BD patients with active and inactive periods. Twelve Behçet patients (6 active and 6 inactive) and 6 control subject were included in the study. Disease activity was considered by clinical findings. Serum and neutrophil samples were obtained from the patients and control subjects. Neutrophils from patients with active BD were divided into three subgroups and were incubated with colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem, respectively. Erythrocyte sedimentation rate, leucocytes counts, serum C-reactive protein, neutrophil, and serum lipid peroxidation and intracellular Ca2+ release levels were higher in active and inactive groups than in the control group, although their levels were lower in active group than in inactive group. However, neutrophil Ca2+ release levels were decreased in colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem groups group compared to active group. Serum glutathione, vitamin A, vitamin E, and β-carotene concentrations were lower in active and inactive groups than in the control group, although serum vitamin E and β-carotene concentrations were higher in the inactive group than in the active group. Neutrophil and serum glutathione peroxidase activity within the three groups did not change. In conclusion, we observed the importance of Ca2+ influx into the neutrophils and oxidative stress in the pathogenesis and activation of the patients with BD. Colchicine induced protective effects on oxidative stress by modulating Ca2+ influx in BD patients. 相似文献