► Quercetin exerts antiproliferative and pro-apoptotic action against human gastric carcinoma cells. ► In sensitive cells cytostatic drug and flavonoid have synergistic effects. ► Quercetin ...supplementation may sensitive resistant cells to cytostatic drug response. ► Quercetin modulates P-glycoprotein expression and its transport function. ► Downregulation of ABCB1 gene is the mechanism of quercetin action on resistant human gastric carcinoma cells.
The benefits of plant polyphenols as chemotherapeutic agents are of great interest due to their possible anti-cancerogenic activities. Results available up to now suggest that flavonoid quercetin induces lethal effect in many types of tumours and may sensitize resistant cells to drugs. The aim of our study was to examine the effect of quercetin on human gastric carcinoma cells and to determine mode of its action. Parental EPG85-257P cell line and its daunorubicin-resistant variant EPG85-257RDB were used as cell models. Our data revealed that quercetin exerted antiproliferative impact on studied cells (with IC50 value of 12μM after 72h), mainly through induction of apoptosis. In sensitive cells cytostatic drug and flavonoid had synergistic effects, in EPG85-257RDB cells quercetin acted as a chemosensitizer. Its impact on resistance mechanism involved decrease of P-glycoprotein expression, inhibition of drug transport and downregulation of ABCB1 gene expression. The results demonstrate that quercetin may be considered as a prospective drug to overcome classical resistance in gastric cancer cells.
•Modified approach for repetitive control based on comb filters.•Introduced multiple normalization factors.•Multiple current harmonics compensation with simple design and implementation.•Stability of ...the main control loop is unaffected.•Introduced FIR filter for robustness improvement
Power quality plays an important role in the operation of grid-connected inverters. The injected current should have a minimum harmonic content in order to comply with the local grid codes. This can be challenging due to the fact that the grid voltage can also be distorted. This paper presents the modified repetitive control method for three-phase grid-connected inverters by means of a digital comb filter application. The proposed method provides multiple harmonics compensation, simple implementation and design. It consists in complementing the Proportional-Resonant (PR) control with an appropriately tuned comb filter, which results in mitigation of the output current harmonics and reduced THD. Two types of comb filters have been proposed as a harmonic compensator, namely feedback and feedforward structures. The compensator included an additional FIR low-pass filter for increased robustness. Regardless of the structure chosen the solution is targeted at simplicity of analysis, design and implementation. Furthermore, the compensator based on the feedforward comb filter is casual, hence its implementation on the digital microprocessors is greatly facilitated. The proposed two-stage design of the control loop ensures the stability even in the case of additional poles being introduced by the feedback comb filter. Investigation on frequency variations impact is also included. The research was conducted by means of the following IT solutions: data workflow management environment, code design and generation (Matlab), and user interface design (ControlDesk). The experimental results have demonstrated the effectiveness of the proposed solution for a grid-connected converter operating in a network with distorted supply voltage.
Abstract
Hybrid taxa from the genus Pelophylax can propagate themselves in a modified way of sexual reproduction called hybridogenesis ensuring the formation of clonal gametes containing the genome ...of only one parental (host) species. Pelophylax grafi from South-Western Europe is a hybrid composed of P. ridibundus and P. perezi genomes and it lives with a host species P. perezi (P-G system). Yet it is unknown, whether non-Mendelian inheritance is fully maintained in such populations. In this study, we characterize P. perezi and P. grafi somatic karyotypes by using comparative genomic hybridization, genomic in situ hybridization, fluorescent in situ hybridization, and actinomycin D-DAPI. Here, we show the homeology of P. perezi and P. grafi somatic karyotypes to other Pelophylax taxa with 2n = 26 and equal contribution of ridibundus and perezi chromosomes in P. grafi which supports F1 hybrid genome constitution as well as a hemiclonal genome inheritance. We show that ridibundus chromosomes have larger regions of interstitial (TTAGGG)n repeats flanking the nucleolus organizing region on chromosome no. 10 and a high quantity of AT pairs in the centromeric regions. In P. perezi, we found species-specific sequences in metaphase chromosomes and marker structures in lampbrush chromosomes. Pericentromeric RrS1 repeat sequence was present in perezi and ridibundus chromosomes, but the blocks were stronger in ridibundus. Various cytogenetic techniques applied to the P-G system provide genome discrimination between ridibundus and perezi chromosomal sets. They could be used in studies of germ-line cells to explain patterns of clonal gametogenesis in P. grafi and broaden the knowledge about reproductive strategies in hybrid animals.
MCM2, MCM3 and MCM7 are minichromosome maintenance proteins found in dividing cells and they play a role in DNA synthesis. Increased MCM expression level is observed in cells of different cancer ...types. Additionally, metallothioneins (MT-I/II) are involved in control of cell proliferation and differentiation and changes of their expression are observed in many types of cancer. Ki-67 is known cancer cell proliferation antigen currently used in prognostic evaluation. The study material consisted of 83 laryngeal squamous cell cancer (LSCC) cases and 10 benign hypertrophic lesions of larynx epithelium as a control group. For the present study, laryngeal cancer cell line HEp-2 and human keratinocytes were employed, and to evaluate expression of all the markers, immunohistochemical method (IHC), immunofluorescence (IF) and western blot analysis were used. Statistical analysis showed strong positive correlation between expression of MCM2, MCM3, MCM7 and Ki-67 antigen in LSCC. Additionally, moderate positive correlation was observed between MCM3 and MT-I/II expression. In cancer cells, the level of expression of MCM3, MCM2, MCM7 and Ki-67 markers was increasing with the grade of LSCC malignancy. IF and western blot analysis showed higher MCM2, MCM3, MCM7 expression in HEp-2 cells in comparison to their expression in keratinocytes. MCM proteins might be useful markers of cell proliferation in LSCC.
Development of road system causes worldwide barriers to wildlife movement and leads to mass road mortality which is a serious threat to the biodiversity, especially globally endangered amphibians. ...Animal carcasses, however, constitute an important non-invasive material for further research including species life history traits, but there is little known whether the road-killed animals are a representative sample of entire population. The aim of our research was to compare the age structures between road-killed and live individuals which crossed the road successfully during the breeding migration. As a model species, we used the common toad
Bufo bufo
which is a main amphibian traffic victim in Europe. We collected toe clips of dead and live toads during their breeding migration in four sampling sites located in the lowlands of western Poland. Phalanges were used for age determination by the skeletochronology. There were no significant differences in age distribution between live and dead individuals of the same sex in all populations studied. In compared groups, medians and mean ages were the same or differed marginally and confidence intervals for the mean age almost completely overlapped. Our results suggest that toads are killed on roads regardless of individual age, thus skeletochronological analysis of dead individuals is useful to study age structure of a live population. Our approach allows to avoid mutilation of amphibians and can be used to increase the knowledge of age structure of a given species living near the road as well as to study long-term road effect on amphibian demography. However, further comparative research on different species is required.
In patients with cirrhosis, only a 75% liver volume (LV) is expected compared with age‑matched healthy individuals. Changes in LV might be an indicator of therapeutic effectiveness or disease ...progression.
To establish whether LV is a prognostic factor in chronic liver disease irrespective of etiology and LV impacts the outcomes of liver transplant (LT).
In total, 135 consecutive LT recipients were prospectively included in this study: 38 women and 97 men. The median (minimum-maximum) age was 51 (21-70) years; body mass index (BMI), 27.3 (17.3-39.2) kg/m2; Child-Pugh class (CPC), C; Model of End‑Stage Liver Disease (MELD), 16 (7-47) points; and the third lumbar vertebra skeletal muscle index (L3SMI), 47.7 (19.7-73.4) cm2/m2. Liver volume and L3SMI were calculated based on computed tomography scans at listing for LT. The receiver operating characteristic (ROC) curve was analyzed to determine the accuracy of LV in mortality prediction after LT.
Liver volume differed significantly among patients in terms of chronic liver disease etiology, with the lowest values noted in those with hepatitis C virus infection. Liver volume was neither a prognostic factor of disease progression and need for LT with respect to the CPC and MELD scores nor correlated with BMI and L3SMI (P >0.05). The area under the ROC curve of LV in mortality prediction was 0.573 (95% CI, 0.403-0.743). Liver volume smaller than the median tended to be positively associated with the risk of prolonged intensive care unit stay and death (P = 0.057 and P = 0.058, respectively).
Low liver volume did not seem be a point of no return in LT candidates.
Human milk, the gold standard in infant nutrition, is a unique fluid that provides essential nutrients such as lactose, lipids, proteins, and free oligosaccharides. While its primary role is ...nutritional, it also protects against pathogens. This protection mainly comes from immunoglobulins, with human milk oligosaccharides (HMOs) providing additional support by inhibiting pathogen binding to host cell ligands. The prebiotic and immune-modulatory activity of HMOs strongly depends on their structure. Over 200 individual structures have been identified so far, with the composition varying significantly among women. The structure and composition of HMOs are influenced by factors such as the Lewis blood group, secretor status, and the duration of nursing. HMO profiles are heavily influenced by maternal phenotypes, which are defined based on the expression of two specific fucosyltransferases. However, recent data have shown that HMO content can be modified by various factors, both changeable and unchangeable, including diet, maternal age, gestational age, mode of delivery, breastfeeding frequency, and race. The first part of this overview presents the historical background of these sugars and the efforts by scientists to extract them using the latest chromatography methods. The second part is divided into subchapters that examine modifiable and non-modifiable factors, reviewing the most recent articles on HMO composition variations due to specific reasons and summarizing potential future challenges in conducting these types of studies.
Metallothioneins I/II (MT) are commonly expressed in mammalian tissues and are highly inducible in the response to stress conditions. Doxorubicin (DOX) intoxication promotes oxidative stress and ...subsequent apoptosis leading to kidney damage. The present study investigates a correlation between endogenous MT expression and DOX-induced apoptosis in renal tubular cells. Experiments were conducted on Buffalo rats receiving DOX (8mg/kg b.w. for 3 weeks) versus control rats injected with saline. The histopathological alterations and apoptosis (TUNEL) were evaluated in tissue sections. MT expression and tissue localization was examined using immunohistochemical method (IHC). Western blot (WB) was used to evaluate pro-caspase-3, active caspase-3 and MT expression level in tissue homogenates. Examination of renal tissue revealed severe nephrotoxicity in DOX-treated animals. Apoptosis was observed in distal convoluted tubular cells, whereas MT was detected in proximal tubular cells. A significant increase in pro-caspase-3, active caspase-3 and MT expression levels (WB) were seen in DOX group. Positive correlations between histopathological lesions, apoptosis and MT expression were observed. The results obtained in this study could suggest the protective and antiapoptotic effect of MT expression in renal proximal tubular cells under DOX intoxication.
Pelophylax esculentus
is the fertile hybrid of
P. ridibundus
and
P. lessonae
. During gametogenesis, one of the parental genomes is removed from the germ line cells, whereas the other one is clonally ...transmitted to the gametes. In hybrids, development of gonads is delayed in comparison with parental species. This may result from complex processes of genome elimination in female tadpoles at Gosner stages 28–46, potentially responsible for increased degeneration of germ cells in developing gonads from the very beginning of sexual differentiation to ovaries with diplotene oocytes, respectively. In this work, we revealed that germ cells died by apoptosis, as detected by expression of active caspase-3 using immunohistochemical method. The main group of degenerating germ cells was primary oogonia, however, in
P. lessonae
and
P. ridibundus
also secondary oogonia and diplotene oocytes were found. The number of degenerating germ cells was significantly higher in ovaries of
P. esculentus
. In hybrids, positive correlations were demonstrated between Gosner stage and gonadal volume, Gosner stage and the number of degenerating germ cells, gonadal volume and number of degenerating germ cells. These observations suggest that increased rate of apoptosis in germ cells, probably as the result of improper genome elimination, may be responsible for delayed maturation of ovaries in
P. esculentus
.
BACKGROUND This study was carried out to evaluate the effects of a long-term high-fat diet on lipids and lipoproteins composition in thoracic duct lymph in pigs. MATERIAL AND METHODS We examined ...lymph taken from the thoracic duct from 24 female white sharp-ear pigs, divided into 3 experimental groups fed different diets for 12 months: (a) the control group, fed the standard balanced diet; (b) the HFD group, fed an unbalanced, high-fat diet, and (c) the reversal diet group (RD), fed an unbalanced, high-fat diet for 9 months and then a standard balanced diet for 3 months. RESULTS Lymph analysis after 12 months of fixed diets revealed significantly higher concentration of proteins in the HFD group in comparison to the control and RD groups. Examination of lymph lipoproteins fractions showed that the high-fat diet in the HFD group in comparison to control group caused an increase in cholesterol, phospholipids, and proteins content within HDL and chylomicrons. There were also more proteins within HDL in the HFD group in comparison to the RD group and more triglycerides within chylomicrons in the HFD group in comparison to the control group. CONCLUSIONS A long-term high-fat diet resulted in changed structure of HDL and chylomicrons in the thoracic duct lymph. Alterations in HDL composition suggest that a high-fat diet enhances reverses cholesterol transport. Changes in chylomicrons structure show the adaptation to more intense transport of dietary fat from the intestine to the liver under the influence of a high-fat diet. Reversal to a standard balanced diet had the opposite effects.
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