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.

Analysis of the antimicrobial potential of sericin-coated silver nanoparticles against human pathogens.

The antibacterial activity of synthetic antimicrobial agents is well known, but most of them have several side effects and are effective against selective microbes. Recently, major concern for the microbiologists is to investigate for some stable, non-toxic, cheap, and eco-friendly antimicrobial agents with a wide range of bactericidal potential. A cost-effective and environmentally friendly alternate has been proposed in the form of green synthesized nanoparticles. The Present study was designed to fabricate sericin-coated silver nanoparticles (S-AgNPs) using sericin as stabilizer and reductant of silver ions and their antibacterial potential was evaluated at various concentrations and temperatures (8, 40, and 50°C). Antimicrobial activities were assessed by the agar well diffusion method. Antibacterial activity of S-AgNPs was measured at different concentrations (1-6 mg/ml) whereas; antifungal activity was tested at 5-20 mg/ml of S-AgNPs. Nanoparticles were characterized by UV-visible spectrophotometer, Fourier transform infrared spectroscopy, and scanning electron microscopy. These nanoparticles significantly subdued the growth of Clostridium difficile (18.7 ± 0.9 mm), Proteus mirabilis (12.3 ± 0.3 mm) and Bacillus licheniformis (10.7 ± 0.9 mm) and Aspergillus flavus (18.7 ± 2.0 mm), Mucor mycetes (13 .0 ± 1.5 mm), Candida albicans (15.3 ± 0.3 mm) and Aspergillus niger (10.0 ± 0.6 mm). S-AgNPs were stable at all temperatures and the maximum growth inhibition was found at 8°C for all pathogenic strains. We concluded that the S-AgNPs could be a potential candidate to inhibit the growth of bacterial and fungal pathogens at a wide range of environmental conditions like temperature. In various biomedical applications including antimicrobial and wound dressings, S-AgNPs can be used in the future to treat various bacterial and fungal infections.

Postharvest shelf life enhancement of peach fruit treated with glucose oxidase immobilized on ZnO nanoparticles.

For the shelf life extension of fruits, we envisioned a novel antimicrobial approach that is based on the production of a thin layer of hydrogen peroxide at the surface of food by utilizing the bioactivity of glucose oxidase (GOx). The enzyme, purified from Aspergillus Niger, was immobilized on zinc oxide nanoparticles and then suspended in a buffer to prepare a spraying solution of GOx/ZnONPs. Post-immobilization analyses indicated that immobilized enzyme showed higher activity as compared to the free enzyme. The GOx/ZnONPs spray was applied for postharvest treatment of peach. The control and treatment groups were stored at ambient conditions for fifteen days and standard quality parameters were analyzed. In contrast to the control group, the GOx/ZnONPs spray treatment was remarkably effective in maintaining the physiological appearance of fruits even more than 12 days and showed a significant reduction in the decrease of weight, firmness, TSS, and DPPH free radical scavenging activity of fruits. Thus GOx/ZnONPs is an excellent platform to extend the postharvest shelf life of peach.

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.

Minocycline-Derived Silver Nanoparticles for Assessment of Their Antidiabetic Potential against Alloxan-Induced Diabetic Mice.

Diabetes is a life-threatening disease, and chronic diabetes affects parts of the body including the liver, kidney, and pancreas. The root cause of diabetes is mainly associated with oxidative stress produced by reactive oxygen species. Minocycline is a drug with a multi-substituted phenol ring and has shown excellent antioxidant activities. The objective of the present study was to investigate the antidiabetic potential of minocycline-modified silver nanoparticles (mino/AgNPs) against alloxan-induced diabetic mice. The mino/AgNPs were synthesized using minocycline as reducing and stabilizing agents. UV-visible, FT-IR, X-ray diffraction (XRD), and transmission electron microscopy (TEM) were applied for the characterization of mino/AgNPs. A 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay was conducted to determine the antioxidant potential of newly synthesized mino/AgNPs. The results revealed that the mino/AgNPs showed higher radical scavenging activity (IC50 = 19.7 µg/mL) compared to the minocycline (IC50 = 26.0 µg/mL) and ascorbic acid (IC50 = 25.2 µg/mL). Further, mino/AgNPs were successfully employed to examine their antidiabetic potential against alloxan-induced diabetic mice. Hematological results showed that the mice treated with mino/AgNPs demonstrated a significant decrease in fasting blood glucose level and lipid profile compared to the untreated diabetic group. A histopathological examination confirmed that the diabetic mice treated with mino/AgNPs showed significant recovery and revival of the histo-morphology of the kidney, central vein of the liver, and islet cells of the pancreas compared to the untreated diabetic mice. Hence, mino/AgNPs have good antidiabetic potential and could be an appropriate nanomedicine to prevent the development of diabetes.

Aging and its treatment with vitamin C: a comprehensive mechanistic review.

Aging and age-related disorders have become one of the prominent issue of world. Oxidative stress due to overproduction of reactive oxygen species is the most significant cause of aging. The aim of literature compilation was to elucidate the therapeutic effect of vitamin C against oxidative stress. Various mediators with anti-inflammatory and anti-oxidant properties might be probable competitors of vitamin C for the improvement of innovative anti-aging treatments. More attention has been paid to vitamin C due to its anti-oxidant property and potentially beneficial biological activities for inhibiting aging.Vitamin C acts as an antioxidant agent and free radical scavenger that can protect the cell from oxidative stress, disorganization of chromatin, telomere attrition, and prolong the lifetime. This review emphasizes mechanism of aging and various biomarkers that are directly related to aging and also focuses on the therapeutic aspect of vitamin C against oxidative stress and age-related disorders.

Identification of a Novel Homozygous Missense (c.443A>T:p.N148I) Mutation in BBS2 in a Kashmiri Family with Bardet-Biedl Syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. METHODS: The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. RESULTS: WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in-silico softwares. CONCLUSION: Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.

Drug-Based Gold Nanoparticles Overgrowth for Enhanced SPR Biosensing of Doxycycline.

In clinical chemistry, frequent monitoring of drug levels in patients has gained considerable importance because of the benefits of drug monitoring on human health, such as the avoidance of high risk of over dosage or increased therapeutic efficacy. In this work, we demonstrate that the drug doxycycline can act as an Au nanoparticle (doxy-AuNP) growth and capping agent to enhance the response of a surface plasmon resonance (SPR) biosensor for this drug. SPR analysis revealed the high sensitivity of doxy-AuNPs towards the detection of free doxycycline. More specifically, doxy-AuNPs bound with protease-activated receptor-1 (PAR-1) immobilized on the SPR sensing surface yield the response in SPR, which was enhanced following the addition of free doxy (analyte) to the solution of doxy-AuNPs. This biosensor allowed for doxycycline detection at concentrations as low as 7 pM. The study also examined the role of colloidal stability and growth of doxy-AuNPs in relation to the response-enhancement strategy based on doxy-AuNPs. Thus, the doxy-AuNPs-based SPR biosensor is an excellent platform for the detection of doxycycline and demonstrates a new biosensing scheme where the analyte can provide enhancement.

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.