36 research outputs found
Propolis Extracts Inhibit UV-Induced Photodamage in Human Experimental In Vitro Skin Models
The aim of this study was to assess the antioxidant, photoprotective, and antiaging effects of Greek propolis. Propolis was subjected to n-heptane or methanol extraction. Total phenolic/flavonoid content and antioxidant potential were determined in the extracts. Promising extracts were evaluated for their cytoprotective properties using human immortalized keratinocyte (HaCaT) or reconstituted human skin tissue following exposure to UVB. Assessment of cytotoxicity, DNA damage, oxidative status, and gene/protein expression levels of various matrix metalloproteinases (MMPs) were performed. The propolis methanolic fractions exhibited higher total phenolic and flavonoid contents and significant in vitro antioxidant activity. Incubation of HaCaT cells with certain methanolic extracts significantly decreased the formation of DNA strand breaks following exposure to UVB and attenuated UVB-induced decrease in cell viability. The extracts had no remarkable effect on the total antioxidant status, but significantly lowered total protein carbonyl content used as a marker for protein oxidation in HaCaT cells. MMP-1, -3, -7, and -9, monitored as endpoints of antiaging efficacy, were significantly reduced by propolis following UVB exposure in a model of reconstituted skin tissue. In conclusion, propolis protects against the oxidative and photodamaging effects of UVB and could be further explored as a promising agent for developing natural antiaging strategies
Multiplex ligation-dependent probe amplification and array comparative genomic hybridization analyses for prenatal diagnosis of cytogenomic abnormalities
First applications of a targeted exome sequencing approach in fetuses with ultrasound abnormalities reveals an important fraction of cases with associated gene defects
Background. Fetal malformations and other structural abnormalities are
relatively frequent findings in the course of routine prenatal
ultrasonographic examination. Due to their considerable genetic and
clinical heterogeneity, the underlying genetic cause is often elusive
and the resulting inability to provide a precise diagnosis precludes
proper reproductive arid fetal risk assessment. We report the
development arid first applications of an expanded exome
sequencing-based test, coupled to a bioinformatics driven prioritization
algorithm, targeting gene disorders presenting with abnormal prenatal
ultrasound findings.
Methods. We applied the testing strategy to14 euploid fetuses, from 11
on-going preg nancies and three products of abortion, all with various
abnormalities or malformations detected through prenatal ultrasound
examination. Whole exome sequencing (WES) was followed by variant
prioritization, utilizing a custom analysis pipeline (Fetalis
algorithm), targeting 758 genes associated with genetic disorders which
may present with abnormal fetal ultrasound findings.
Results. A definitive or highly-likely diagnosis was made in 6 of 14
cases (43%), of which 3 were abortuses (Ellis-van Creveld syndrome,
Ehlers-Danlos syndrome and Nemaline myopathy 2) and 3 involved on-going
pregnancies (Citrullinemia, Noonan syndrome, PROKR2-related Kallmann
syndrome). In the remaining eight on-going pregnancy cases (57%), a
ZICI variant of unknown clinical significance was detected in one case,
while in seven cases testing did not reveal any pathogenic variant(s).
Pregnancies were followed-up to birth, resulting in one neonate
harboring the PROKR2 mutation, presenting with isolated minor structural
cardiac abnormalities, and in seven apparently healthy neonates.
Discussion. The expanded targeted exome sequencing-based approach
described herein (Fetall s), provides strong evidence suggesting a
definite and beneficial increase in our diagnostic capabilities in
prenatal diagnosis of otherwise chromosomally balanced fetuses with
troubling ultrasound abnormalities.Furthermore, the proposed targeted
exome sequencing strategy, designed primarily as a diagnostic rather
than a research discovery tool, overcomes many of the problems and
limitations associated with clinical wide-scale WES testing in a
prenatal setting
First applications of a targeted exome sequencing approach in fetuses with ultrasound abnormalities reveals an important fraction of cases with associated gene defects
Background. Fetal malformations and other structural abnormalities are relatively frequent findings in the course of routine prenatal ultrasonographic examination. Due to their considerable genetic and clinical heterogeneity, the underlying genetic cause is often elusive and the resulting inability to provide a precise diagnosis precludes proper reproductive and fetal risk assessment. We report the development and first applications of an expanded exome sequencing-based test, coupled to a bioinformatics-driven prioritization algorithm, targeting gene disorders presenting with abnormal prenatal ultrasound findings. Methods. We applied the testing strategy to14 euploid fetuses, from 11 on-going pregnancies and three products of abortion, all with various abnormalities or malformations detected through prenatal ultrasound examination. Whole exome sequencing (WES) was followed by variant prioritization, utilizing a custom analysis pipeline (Fetalis algorithm), targeting 758 genes associated with genetic disorders which may present with abnormal fetal ultrasound findings. Results. A definitive or highly-likely diagnosis was made in 6 of 14 cases (43%), of which 3 were abortuses (Ellis-van Creveld syndrome, Ehlers-Danlos syndrome and Nemaline myopathy 2) and 3 involved on-going pregnancies (Citrullinemia, Noonan syndrome, PROKR2-related Kallmann syndrome). In the remaining eight on-going pregnancy cases (57%), a ZIC1 variant of unknown clinical significance was detected in one case, while in seven cases testing did not reveal any pathogenic variant(s). Pregnancies were followed-up to birth, resulting in one neonate harboring the PROKR2 mutation, presenting with isolated minor structural cardiac abnormalities, and in seven apparently healthy neonates. Discussion. The expanded targeted exome sequencing-based approach described herein (Fetalis), provides strong evidence suggesting a definite and beneficial increase in our diagnostic capabilities in prenatal diagnosis of otherwise chromosomally balanced fetuses with troubling ultrasound abnormalities. Furthermore, the proposed targeted exome sequencing strategy, designed primarily as a diagnostic rather than a research discovery tool, overcomes many of the problems and limitations associated with clinical wide-scale WES testing in a prenatal setting
A familial case of Muenke syndrome. Diverse expressivity of the FGFR3 Pro252Arg mutation - case report and review of the literature
Muenke is a fibroblast growth factor receptor 3 (FGFR-3)-associated
syndrome, which was first described in late 1990s. Muenke syndrome is an
autosomal dominant disorder characterized mainly by coronal suture
craniosynostosis, hearing impairment and intellectual disability. The
syndrome is defined molecularly by a unique point mutation c.749C>G in
exon 7 of the FGFR3 gene which results to an amino acid substitution p.
Pro250Arg of the protein product. Despite the fact that the mutation
rate at this nucleotide is one of the most frequently described in human
genome, few Muenke familial case reports are published in current
literature. We describe individuals among three generations of a Greek
family who are carriers of the same mutation. Medical record and
physical examination of family members present a wide spectrum of
clinical manifestations. In particular, a 38-year-old woman and her
father appear milder clinical findings regarding craniofacial
characteristics compared to her uncle and newborn female child. This
familial case illustrates the variable expressivity of Muenke syndrome
in association with an identical gene mutation
Cloned cDNA for rabbit erythrocyte carbonic anhydrase I: A novel erythrocyte-specific probe to study development in erythroid tissues.
The prenatal diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) by mutation analysis
Cerebral autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL) is an important cause of hereditary
stroke. Mutations in the Notch3 gene are clearly causally linked to this
progressive vascular disorder. Cerebral ischemic attacks, cognitive
decline, strokes, and vascular dementia constitute the major
manifestations of this disorder. This report details the prenatal
detection of a Notch3 mutation in the fetus of a couple where the father
had a known mutation in this gene. This is the first report of a
prenatal diagnosis of CADASIL, and another example of a serious, highly
penetrant, and relentlessly progressive degenerative genetic disorder
presenting decades after birth and for which prenatal diagnosis is an
option. Copyright (c) 2005 John Wiley & Sons, Ltd
Human embryo twinning with proof of monozygocity
Objective: To prove monozygocity of human twin blastocysts derived from embryo splitting at the cleavage stage.
Methods: Human triploid embryos at the 6–8 cell stage were split into twin embryos (D and R) and cultured in vitro to the blastocyst stage. Twin embryos were processed for nested multiplex PCR using fluorescently labeled primers of six selected polymorphic STR markers within the human HLA locus.
Results: A total of 11 pairs of twin embryos were analyzed with PCR technology. From five pairs of twin blastocysts, the fluorograms provided detectable STR profiles for identical peak position between the twin embryos.
Conclusion: This is the first report on twinned human embryos to prove monozygocity at the DNA level. Embryo splitting exhibits novel potential for future applications in assisted reproductive medicine