A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.

EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.

Current status of beta-thalassemia and its treatment strategies.

BACKGROUND: Thalassemia is an inherited hematological disorder categorized by a decrease or absence of one or more of the globin chains synthesis. Beta-thalassemia is caused by one or more mutations in the beta-globin gene. The absence or reduced amount of beta-globin chains causes ineffective erythropoiesis which leads to anemia. METHODS: Beta-thalassemia has been further divided into three main forms: thalassemia major, intermedia, and minor/silent carrier. A more severe form among these is thalassemia major in which individuals depend upon blood transfusion for survival. The high level of iron deposition occurs due to regular blood transfusion therapy. RESULTS: Overloaded iron raises the synthesis of reactive oxygen species (ROS) that are noxious and prompting the injury to the hepatic, endocrine, and vascular system. Thalassemia can be analyzed and diagnosed via prenatal testing (genetic testing of amniotic fluid), blood smear, complete blood count, and DNA analysis (genetic testing). Treatment of thalassemia intermediate is symptomatic; however; it can also be accomplished by folic supplementation and splenectomy. CONCLUSION: Thalassemia major can be cured through regular transfusion of blood, transplantation of bone marrow, iron chelation management, hematopoietic stem cell transplantation, stimulation of fetal hemoglobin production, and gene therapy.

Novel Biosynthesis of Copper Nanoparticles Using Zingiber and Allium sp. with Synergic Effect of Doxycycline for Anticancer and Bactericidal Activity.

Copper nanoparticles (CuNPs), due to their cost-effective synthesis, interesting properties, and a wide range of applications in conductive inks, cooling fluids, biomedical field, and catalysis, have attracted the attention of scientific community in recent years. The aim of the present study was to develop and characterize antibacterial and anticancer CuNPs synthesized via chemical and biological methods, and further synthesize CuNPs conjugated with doxycycline to study their synergic effect. During the chemical synthesis, ascorbic acid was used as a stabilizing agent, while Zingiber officinale and Allium sativum-derived extracts were used during the biological methods for synthesis of CuNPs. Characterization of CuNPs was performed by transmission electron microscopy (TEM), UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray crystallography (XRD). Antimicrobial evaluation of the nanomaterials against Pseudomonas aeruginosa and Escherichia coli was performed by using disk diffusion method, while anticancer behavior against HeLa and HepG2 cell lines was studied by MTT assay. TEM revealed spherical-shaped nanoparticles with mean size of 22.70 ± 5.67, 35.01 ± 5.84, and 19.02 ± 2.41 nm for CuNPs, Gin-CuNPs, and Gar-CuNPs, respectively, and surface plasmon resonance peaks were obtained at 570 nm, 575 nm, and 610 nm for CuNPs, Gar-CuNPs, and Gin-CuNPs, respectively. The results of FTIR confirmed the consumption of biomolecules from the plant extracts for the synthesis of CuNPs. XRD analysis also confirmed synthesis of CuNPs. Doxycycline-conjugated NPs exhibited more antibacterial effects than doxycycline or CuNPs alone. Copper nanoparticles prepared by biological synthesis are cost-effective and eco-friendly as compared to their chemical counterparts. The chemically synthesized nanoparticles displayed more significant antimicrobial activity when capped with doxycycline than Z. officinale and A. sativum-mediated CuNPs; however, green-synthesized nanoparticles showed greater anticancer activity than their chemical counterparts.

In Vitro Drug Release and Biocatalysis from pH-Responsive Gold Nanoparticles Synthesized Using Doxycycline.

pH-sensitive doxycycline gold nanoparticles (doxy-AuNPs) are reported here to act as effective drug nanocarriers and as biocatalysts. The AuNPs were synthesized with doxy as the reducing and capping agent. Various parameters were optimized to find the best conditions for the synthesis of doxy-AuNPs, and these were characterized with UV-vis, X-ray diffraction (XRD), FTIR, and transmission electron microscopy (TEM). Doxy-AuNPs were then loaded with the anticancer drug doxorubicin (DOX), where 70% of the initially available drug was loaded within 24 h. Furthermore, pH-dependent drug release was measured at 60% with in vitro measurements in phosphate-buffered saline (PBS). In addition, the doxy-AuNPs were applied as a biocatalyst. Oxidation of dopamine was taken as a model reaction to determine the catalytic activity of doxy-AuNPs. Almost complete oxidation of dopamine occurred in 5 min, which indicates the fast response of synthesized doxy-AuNPs as a biocatalyst. Hence, doxy-AuNPs are a versatile platform for drug loading and biocatalyst.