Gentiopicroside (GPS) is a leading component of several plant species from the Gentianaceae botanical family. As a compound with plenty of biological activities and a component of herbal drugs, GPS ...has an important role in the regulation of physiological processes in humans. The results of recently published scientific studies underline a meaningful role of this molecule as an active factor in metabolic pathways and mechanisms, which may have an influence in the treatment of different diseases, including digestive tract disorders, malignant changes, neurological disorders, microbial infections, bone formation disorders, inflammatory conditions, and others. This review aims to collect previously published reports on the biological properties of GPS as a single compound that were confirmed by
and
studies, and to draw attention to the newly discovered role of this bitter-tasting secoiridoid. Thanks to these properties, the research on this substance could be revisited.
Widespread worldwide Peucedanum plants (Apiaceae) have been used for centuries as plant medicines. The polymorphism of this genus is consistent with chemotaxonomically and therapeutically significant ...differences in the composition of secondary metabolites. GC-MS of Peucedanum tauricum M.B. volatiles from the headspace (HS) and hydrodistilled essential oil (HD), both obtained simultaneously from flowers (FL), immature and ripe fruits (IF, MF) and leaves (L1-L3) collected at the time of harvesting of generative organs, show differences in the chemical profiles of HS and HD from the same parts of the plant, and between organs (FL, IF, MF vs. L1-L3). The presented studies on the variability of biometabolites in the phenological period indicated the optimal harvesting time, focused on two molecular chemotaxonomic markers of PT; guaia-1(10),11-diene and guaia-9,11-diene (in generative organs iHD at 25.5–32.1% and 26.8–33.6%; and in their HS at 29.4–41.3% and 25.0–29.4%, respectively). This is the first report on the analysis of fresh aerial parts of Peucedanum sp. in which GC-MS of HS and HD was performed simultaneously during the vegetation period. The importance, with possible limitations, of GC-MS analysis of HS and HD as an evaluation tool useful in the chemotaxonomy of Peucedanum plants was also discussed.
Summary
Objective
Copy number variations (CNVs) represent a significant genetic risk for several neurodevelopmental disorders including epilepsy. As knowledge increases, reanalysis of existing data ...is essential. Reliable estimates of the contribution of CNVs to epilepsies from sizeable populations are not available.
Methods
We assembled a cohort of 1255 patients with preexisting array comparative genomic hybridization or single nucleotide polymorphism array based CNV data. All patients had “epilepsy plus,” defined as epilepsy with comorbid features, including intellectual disability, psychiatric symptoms, and other neurological and nonneurological features. CNV classification was conducted using a systematic filtering workflow adapted to epilepsy.
Results
Of 1097 patients remaining after genetic data quality control, 120 individuals (10.9%) carried at least one autosomal CNV classified as pathogenic; 19 individuals (1.7%) carried at least one autosomal CNV classified as possibly pathogenic. Eleven patients (1%) carried more than one (possibly) pathogenic CNV. We identified CNVs covering recently reported (HNRNPU) or emerging (RORB) epilepsy genes, and further delineated the phenotype associated with mutations of these genes. Additional novel epilepsy candidate genes emerge from our study. Comparing phenotypic features of pathogenic CNV carriers to those of noncarriers of pathogenic CNVs, we show that patients with nonneurological comorbidities, especially dysmorphism, were more likely to carry pathogenic CNVs (odds ratio = 4.09, confidence interval = 2.51‐6.68; P = 2.34 × 10−9). Meta‐analysis including data from published control groups showed that the presence or absence of epilepsy did not affect the detected frequency of CNVs.
Significance
The use of a specifically adapted workflow enabled identification of pathogenic autosomal CNVs in 10.9% of patients with epilepsy plus, which rose to 12.7% when we also considered possibly pathogenic CNVs. Our data indicate that epilepsy with comorbid features should be considered an indication for patients to be selected for a diagnostic algorithm including CNV detection. Collaborative large‐scale CNV reanalysis leads to novel declaration of pathogenicity in unexplained cases and can promote discovery of promising candidate epilepsy genes.
Congenital heart defects (CHDs) appear in 8-10 out of 1000 live born newborns and are one of the most common causes of deaths. In fetuses, the congenital heart defects are found even 3-5 times more ...often. Currently, microarray comparative genomic hybridization (array CGH) is recommended by worldwide scientific organizations as a first-line test in the prenatal diagnosis of fetuses with sonographic abnormalities, especially cardiac defects. We present the results of the application of array CGH in 484 cases with prenatally diagnosed congenital heart diseases by fetal ultrasound scanning (256 isolated CHD and 228 CHD coexisting with other malformations). We identified pathogenic aberrations and likely pathogenic genetic loci for CHD in 165 fetuses and 9 copy number variants (CNVs) of unknown clinical significance. Prenatal array-CGH is a useful method allowing the identification of all unbalanced aberrations (number and structure) with a much higher resolution than the currently applied traditional assessment techniques karyotype. Due to this ability, we identified the etiology of heart defects in 37% of cases.
It is well known that the rate of arterial hypertension (AH) in childhood acute lymphoblastic leukemia (ALL) survivors is significantly higher than that in the healthy pediatric population; however, ...the mechanism of this phenomenon is not fully understood. The developing cardiovascular system in children is thought to be highly susceptible to the toxic effects of chemotherapy, which causes damage to the blood vessel wall, including the endothelium. Endothelin-1 (ET-1) is a marker of endothelial damage, and it contributes to AH. Endothelial progenitor cells (EPCs) are derived from the bone marrow and participate in the process of blood vessel repair. The aim of this study was to determine the relationship between the rate of circulating EPCs and plasma levels of ET-1 with respect to hypertension in childhood ALL survivors. The study included 88 childhood ALL survivors and 44 healthy children as controls. All patients and controls had 24-h blood pressure monitoring with a HolCARD CR-07 device. The number of EPCs and the ET-1 serum concentration were measured in the peripheral blood of patients and controls using flow cytometry and enzyme-linked immunosorbent assay, respectively. A correlation was found between the number of EPCs and the ET-1 concentration in the peripheral blood of healthy children and normotensive ALL survivors. However, such a correlation was not found in hypertensive childhood ALL survivors. We conclude that dysregulation of the 'ET-1 and EPC axis' may contribute to the development of AH in some childhood ALL survivors.
Aerial parts and roots of Crithmum maritimum L. fertilized with Tytanit were investigated on the presence of phenolic acids (PhAs). Cinnamic and benzoic acid derivatives were quantified by use of ...validated RP-HPLC/DAD method. The amount of PhAs in fertilized plants (T) was higher than in control (C) plants (in the aerial parts: 2.16 mg/g and 1.28 mg/g dry weight, respectively, and in roots: 4.05 mg/g and 2.78 mg/g dry weight, respectively). The predominant PhA was the caffeic acid (83.2–94.2% of the total PhAs). After Tytanit treatment, amount of the caffeic acid rose from 667.41 µg/g in C to 1463.83 µg/g dry weight in the aerial parts of T, and in roots from 2251.74 µg/g in C to 3451.86 µg/g dry weight in T. Tytanit had also influence on the qualitative composition of PhAs; in extracts from aerial parts, some of PhAs (ferulic, chlorogenic, and syringic acids), absent in control, appeared after fertilization.
Cytogenomic features of Richter transformation Woroniecka, Renata; Rymkiewicz, Grzegorz; Bystydzienski, Zbigniew ...
Molecular cytogenetics,
11/2023, Volume:
16, Issue:
1
Journal Article
Peer reviewed
Open access
Abstract
Background
Richter transformation (RT) is the development of aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This rare disease is ...characterised by dismal prognosis. In recent years, there has been a deeper understanding of RT molecular pathogenesis, and disruptions of apoptosis (
TP53
) and proliferation (
CDKN2A, MYC, NOTCH1
) has been described as typical aberrations in RT.
Results
A single-institution cohort of 33 RT patients were investigated by karyotyping, fluorescence in situ hybridization and single nucleotide polymorphism/copy number (CN) arrays. Most of RTs were typically manifested by diffuse large B-cell lymphoma, not otherwise specified, among the remaining cases one was classified as high-grade B-cell lymphoma with 11q aberrations. The most frequent alterations (40–60% of cases) were represented by
MYC
rearrangement/gain, deletions of
TP53
and
CDKN2A
,
IGH
rearrangement and 13q14 deletion. Several other frequent lesions included losses of 14q24.1-q32.33, 7q31.33-q36.3, and gain of 5q35.2. Analysis of 13 CLL/SLL-RT pairs showed that RT arised from the CLL/SLL by acquiring of 10 ~ 12 cytogenetic or CN lesions/case, but without acquisition of loss of heterozygosity regions. Our result affirmed the higher genetic complexity in RT than CLL/SLL and confirmed the linear features of RT clonal evolution as predominant.
Conclusions
Cytogenomic profile was concordant with the literature data, however the role of
IGH
rearrangement, 14q deletion and 5q35.2 gain need to be explored. We anticipate that further characterization of RT lesions will probably facilitate better understanding of the RT clonal evolution.
Mutations in the CDKL5 gene have been associated with an X-linked dominant early infantile epileptic encephalopathy-2. The clinical presentation is usually of severe encephalopathy with refractory ...seizures and Rett syndrome (RTT)-like phenotype. We attempted to assess the role of mosaic intragenic copy number variation in CDKL5.
We have used comparative genomic hybridization with a custom-designed clinical oligonucleotide array targeting exons of selected disease and candidate genes, including CDKL5.
We have identified mosaic exonic deletions of CDKL5 in one male and two females with developmental delay and medically intractable seizures. These three mosaic changes represent 60% of all deletions detected in 12,000 patients analyzed by array comparative genomic hybridization and involving the exonic portion of CDKL5.
We report the first case of an exonic deletion of CDKL5 in a male and emphasize the importance of underappreciated mosaic exonic copy number variation in patients with early-onset seizures and RTT-like features of both genders.
Most genetic disorders, especially rare and manifested with an unspecific constellation of developmental anomalies, are challenging to diagnose before birth. The paper aims to present a rare case of ...terminal 21q22 deletion to extend the knowledge on this rare genetic disease, mostly to facilitate prenatal guidance by pointing the diagnostic features.
The fetus was diagnosed prenatally, at 21 weeks of gestation, due to ultrasound markers detected in a routine ultrasound scan. Post-mortem dysmorphological assessment has verified the diagnosis. To the best of our knowledge, this is the second report of prenatal presentation of partial monosomy 21q.
By giving the detailed phenotype description and presenting a comprehensive literature review on the subject, we delineate its phenotype, which was different from what has been shown in the literature. Specifically, the clinical presentation of aberration within regions 2 and 3 (referring to the term proposed by Lyle et al., in 2009) of 21q22 bands is not characterised by multiple or severe malformations, which matters for prenatal counselling and diagnostics.
The aim of this study was to determine the suitability of the comparative genomic hybridization to microarray (aCGH) technique for prenatal diagnosis, but also to assess the frequency of chromosomal ...aberrations that may lead to fetal malformations but are not included in the diagnostic report. We present the results of the aCGH in a cohort of 7400 prenatal cases, indicated for invasive testing due to ultrasound abnormalities, high-risk for serum screening, thickened nuchal translucency, family history of genetic abnormalities or congenital abnormalities, and advanced maternal age (AMA). The overall chromosomal aberration detection rate was 27.2% (2010/7400), including 71.2% (1431/2010) of numerical aberrations and 28.8% (579/2010) of structural aberrations. Additionally, the detection rate of clinically significant copy number variants (CNVs) was 6.8% (505/7400) and 0.7% (57/7400) for variants of unknown clinical significance. The detection rate of clinically significant submicroscopic CNVs was 7.9% (334/4204) for fetuses with structural anomalies, 5.4% (18/336) in AMA, 3.1% (22/713) in the group of abnormal serum screening and 6.1% (131/2147) in other indications. Using the aCGH method, it was possible to assess the frequency of pathogenic chromosomal aberrations, of likely pathogenic and of uncertain clinical significance, in the groups of cases with different indications for an invasive test.
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