Hepatic stellate cells (HSCs) are located in the space of Disse, between liver sinusoidal endothelia cells (LSECs) and hepatocytes. They have surprised and excited hepatologists for their biological characteristics. Under physiological quiescent conditions, HSCs are the major vitamin A-storing cells of the liver, playing crucial roles in the liver development, regeneration, and tissue homeostasis. Upon injury-induced activation, HSCs convert to a pro-fibrotic state, producing the excessive extracellular matrix (ECM) and promoting angiogenesis in the liver fibrogenesis. Activated HSCs significantly contribute to liver fibrosis progression and inactivated HSCs are key to liver fibrosis regression. In this review, we summarize the comprehensive understanding of HSCs features, including their roles in normal liver and liver fibrosis in hopes of advancing the development of emerging diagnosis and treatment for hepatic fibrosis.
- MeSH
- jaterní cirhóza etiologie MeSH
- jaterní hvězdicovité buňky fyziologie ultrastruktura MeSH
- játra embryologie MeSH
- lidé MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: In this study we detail the effect of different fixation agents and the duration of storage has on the immunohistochemical staining positivity of samples of archival embryonic and fetal tissues. MATERIALS AND METHODS: The samples were stained by indirect two-step immunohistochemistry (IHC) method for Ki-67, cyclin A and β-actin. RESULTS: Irrespective of the length of tissue archiving, tissue fixation with 10% neutral buffered formalin had better IHC intensity results in all cases when compared to methacarn-fixed tissues. In the case of β-actin, this difference was statistically significant, while differences in Ki-67 and cyclin A were not. The second aspect studied was which effect tissue block archiving duration has on the IHC reactivity. We demonstrated a statistically significant decrease in IHC positivity for all studied antigens between the samples that were archived for 10-19 or 20-45 years, regardless the fixative solution. CONCLUSION: To the best of our knowledge, the influence that the duration of tissue block archiving has on IHC positivity in human embryo and fetal tissue material has not yet been studied. Although the causes of the IHC positivity decline in archived tissue blocks are not well understood, a possible decrease in IHC over time should be considered, particularly in retrospective studies.
- Klíčová slova
- Archive tissue samples, Fixation, Immunohistochemistry, Quality of tissue samples,
- MeSH
- aktiny analýza MeSH
- antigen Ki-67 analýza MeSH
- barvení a značení normy MeSH
- časové faktory MeSH
- chloroform MeSH
- cyklin A analýza MeSH
- fixace tkání metody MeSH
- fixativa MeSH
- formaldehyd MeSH
- gestační stáří MeSH
- imunohistochemie normy MeSH
- játra embryologie MeSH
- králíci MeSH
- kyselina octová MeSH
- lidé MeSH
- methanol MeSH
- myši MeSH
- placenta embryologie MeSH
- střeva embryologie MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aktiny MeSH
- antigen Ki-67 MeSH
- chloroform MeSH
- cyklin A MeSH
- fixativa MeSH
- formaldehyd MeSH
- kyselina octová MeSH
- methacarn MeSH Prohlížeč
- methanol MeSH
Tissue differentiation and proliferation throughout fetal development interconnect with changes in the oxidative phosphorylation system (OXPHOS) on the cellular level. Reevaluation of the expression data revealed a significant increase in COX4 and MTATP6 liver transcription levels after the 22(nd) gestational week (GW) which inspired us to characterize its functional impact. Specific activities of cytochrome c oxidase (COX), citrate synthase (CS), succinate-coenzyme Q reductase (SQR) and mtDNA determined by spectrophotometry and RT-PCR were studied in a set of 25 liver and 18 skeletal muscle samples at 13(th) to 29(th) GW. Additionally, liver hematopoiesis (LH) was surveyed by light microscopy. The mtDNA content positively correlated with the gestational age only in the liver. The activities of COX, CS and SQR in both liver and muscle isolated mitochondria significantly decreased after the 22(nd) GW in comparison with earlier GW. A continuous decline of LH, not correlating with the documented OXPHOS-specific activities, was observed from the 14(th) to the 24(th) GW indicating their exclusive reflection of liver tissue processes. Two apparently contradictory processes of increasing mtDNA transcription and decreasing OXPHOS-specific activities seem to be indispensable for rapid postnatal adaptation to high energy demands. The inadequate capacity of mitochondrial energy production may be an important factor in the mortality of children born before the critical developmental point of the 22(nd) GW.
- MeSH
- citrátsynthasa biosyntéza genetika MeSH
- genetická transkripce fyziologie MeSH
- játra embryologie metabolismus MeSH
- kosterní svaly embryologie metabolismus MeSH
- lidé MeSH
- respirační komplex II biosyntéza genetika MeSH
- respirační komplex IV biosyntéza genetika MeSH
- těhotenství MeSH
- vývoj plodu fyziologie MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- citrátsynthasa MeSH
- respirační komplex II MeSH
- respirační komplex IV MeSH
OBJECTIVES: Respiratory morbidity in congenital diaphragmatic hernia (CDH) is associated with high mortality and adverse outcome. Accurate prenatal diagnosis is essential for prognosis and potential treatment in utero. The aim was to evaluate the prenatal ultrasound findings in assessing the respiratory prognosis in fetuses with isolated left-sided CDH. METHODS: We retrospectively analyzed the medical records of 59 prenatally diagnosed left-sided CDH cases managed at a tertiary perinatal center. RESULTS: Survival rate in the study group was 73% (43/59). We found no statistically significant relationship between survival and the presence of polyhydramnios, gestational age at diagnosis, lung-to-head ratio (LHR) and observed/expected LHR (O/E LHR) values, gestational age at birth and birth weight. Intrathoracic liver herniation was a statistically significant parameter adversely affecting survival (37.2% in survivors, 68.8% in non-survivors, p = 0.031) and logistic regression confirmed this relationship. The presence of pneumothorax and severe pulmonary hypertension were significantly associated with mortality (82% non-survivors versus 15% in survivors, p = 0.0001). CONCLUSION: Intrathoracic liver herniation seems to be a reliable parameter in the prediction of survival and neonatal respiratory morbidity in fetuses with isolated left-sided CDH. In contrast, we found no significant correlation between perinatal outcome and LHR, O/E LHR values, birth weight and gestational age.
- Klíčová slova
- Congenital diaphragmatic hernia, outcome, prenatal diagnosis, respiratory morbidity,
- MeSH
- gestační stáří MeSH
- hlava diagnostické zobrazování embryologie MeSH
- játra diagnostické zobrazování embryologie MeSH
- lidé MeSH
- logistické modely MeSH
- plíce diagnostické zobrazování embryologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- ultrasonografie prenatální * MeSH
- vrozená brániční kýla diagnóza embryologie mortalita MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The sensitivity of early life stages of common carp (Cyprinus carpio L.) to chronic exposure to single and combined environmental concentrations of the triazine metabolites terbuthylazine 2-hydroxy, terbuthylazine-desethyl and atrazine 2-hydroxy was evaluated under laboratory conditions. Their effects were assessed on lipid peroxidation, antioxidant enzymes (total superoxide dismutase, glutathione reductase, catalase, glutathione S-transferase, reduced glutathione), mortality, growth, development and histology. Single metabolites (terbuthylazine 2-hydroxy-0.73 μg/L; terbuthylazine-desethyl-1.80 μg/L; atrazine 2-hydroxy-0.66 μg/L) and combinations were not associated with negative effects on hatching, behaviour, embryo viability, growth or early ontogeny. Carp exposed to terbuthylazine-desethyl at 1.80 μg/L showed significantly lower total superoxide dismutase and glutathione reductase activity compared with the control group. Liver histology revealed diffused steatosis associated with the presence of lipid inclusions in hepatic cells in groups exposed to terbuthylazine-desethyl, atrazine 2-hydroxy and the tested combination of metabolites.
- Klíčová slova
- Antioxidant enzymes, Atrazine 2-hydroxy, Fish, Terbuthylazine 2-hydroxy, Terbuthylazine-desethyl,
- MeSH
- antioxidancia metabolismus MeSH
- atrazin metabolismus toxicita MeSH
- chemické látky znečišťující vodu metabolismus toxicita MeSH
- embryo nesavčí účinky léků enzymologie metabolismus MeSH
- glutathion metabolismus MeSH
- glutathionreduktasa metabolismus MeSH
- glutathiontransferasa metabolismus MeSH
- herbicidy metabolismus toxicita MeSH
- játra účinky léků embryologie patologie MeSH
- kapři embryologie metabolismus MeSH
- katalasa metabolismus MeSH
- látky reagující s kyselinou thiobarbiturovou metabolismus MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- superoxiddismutasa metabolismus MeSH
- triaziny metabolismus toxicita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia MeSH
- atrazin MeSH
- chemické látky znečišťující vodu MeSH
- glutathion MeSH
- glutathionreduktasa MeSH
- glutathiontransferasa MeSH
- herbicidy MeSH
- katalasa MeSH
- látky reagující s kyselinou thiobarbiturovou MeSH
- superoxiddismutasa MeSH
- terbutylazine MeSH Prohlížeč
- triaziny MeSH
During the process of intra-uterine mammalian fetal development, the oxygen supply in growing fetus is low. A rapid switch from glycolysis-based metabolism to oxidative phosphorylation (OXPHOS) must proceed during early postnatal adaptation to extra-uterine conditions. Mitochondrial biogenesis and mammalian mitochondrial F(o)F(1)-ATP synthase assembly (complex V, EC 3.6.3.14, ATPase) are complex processes regulated by multiple transcription regulators and assembly factors. Using RNA expression analysis of rat liver and skeletal tissue (Rattus norvegicus, Berkenhout, 1769), we describe the expression profiles of 20 genes involved in mitochondrial maturation and ATP synthase biogenesis in detail between the 16th and 22nd day of gestation and the first 4 days of life. We observed that the most important expression shift occurred in the liver between the 20th and 22nd day of gestation, indicating that the fetus prepares for birth about two days before parturition. The detailed mechanism regulating the perinatal adaptation process is not yet known. Deeper insights in perinatal physiological development will help to assess mitochondrial dysfunction in the broader context of cell metabolism in preterm newborns or neonates with poor adaptation to extra-uterine life.
- MeSH
- biogeneze organel MeSH
- fyziologická adaptace * MeSH
- játra embryologie růst a vývoj metabolismus MeSH
- novorozená zvířata růst a vývoj metabolismus MeSH
- pilotní projekty MeSH
- potkani Wistar MeSH
- protonové ATPasy biosyntéza MeSH
- stanovení celkové genové exprese MeSH
- svaly embryologie metabolismus MeSH
- těhotenství MeSH
- vývoj svalů MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- protonové ATPasy MeSH
The mammalian circadian system develops gradually during ontogenesis, and after birth, the system is already set to a phase of the mothers. The role of maternal melatonin in the entrainment of fetal circadian clocks has been suggested, but direct evidence is lacking. In our study, intact or pinealectomized pregnant rats were exposed to constant light (LL) throughout pregnancy to suppress the endogenous melatonin and behavioral rhythms. During the last 5 days of gestation, the rats were injected with melatonin or vehicle or were left untreated. After delivery, daily expression profiles of c-fos and Avp in the suprachiasmatic nuclei (SCN), and Per1, Per2, Rev-erbα, and Bmal1 in the liver were measured in 1-day-old pups. Due to the LL exposure, no gene expression rhythms were detected in the SCN of untreated pregnant rats or in the SCN and liver of the pups. The administration of melatonin to pregnant rats entrained the pups' gene expression profiles in the SCN, but not in the liver. Melatonin did not affect the maternal behavior during pregnancy. Vehicle injections also synchronized the gene expression in the SCN but not in the liver. Melatonin and vehicle entrained the gene expression profiles to different phases, demonstrating that the effect of melatonin was apparently not due to the treatment procedure per se. The data demonstrate that in pregnant rats with suppressed endogenous melatonin levels, pharmacological doses of melatonin affect the fetal clock in the SCN but not in the liver.
- Klíčová slova
- circadian system, clock gene, melatonin, ontogenesis, suprachiasmatic nuclei,
- MeSH
- arginin vasopresin metabolismus MeSH
- cirkadiánní hodiny fyziologie MeSH
- cirkadiánní proteiny Period metabolismus MeSH
- jaderné receptory - podrodina 1, skupina D, člen 1 metabolismus MeSH
- játra embryologie fyziologie MeSH
- kortikosteron krev MeSH
- krysa rodu Rattus MeSH
- mateřské chování fyziologie MeSH
- melatonin metabolismus MeSH
- novorozená zvířata MeSH
- nucleus suprachiasmaticus embryologie fyziologie MeSH
- pohybová aktivita fyziologie MeSH
- potkani Wistar MeSH
- protoonkogenní proteiny c-fos metabolismus MeSH
- světlo MeSH
- transkripční faktory ARNTL metabolismus MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- arginin vasopresin MeSH
- Arntl protein, rat MeSH Prohlížeč
- cirkadiánní proteiny Period MeSH
- jaderné receptory - podrodina 1, skupina D, člen 1 MeSH
- kortikosteron MeSH
- melatonin MeSH
- Nr1d1 protein, rat MeSH Prohlížeč
- Per1 protein, rat MeSH Prohlížeč
- Per2 protein, rat MeSH Prohlížeč
- protoonkogenní proteiny c-fos MeSH
- transkripční faktory ARNTL MeSH
There is growing evidence that some members of cytochrome P450 enzymes contribute to regulation of normal prenatal development. CYP epoxygenases (CYP2C and CYP2J subfamilies) convert arachidonic acid into four regioisomeric epoxyeicosatrienoic acids (EETs), biologically active molecules involved in mitogenesis and cell signaling. Almost nothing is known about localization of their expression in tissues during human prenatal development. The spatio-temporal expression pattern of CYP2C8, CYP2C9, CYP2C19 and CYP2J2 in human embryonic/fetal intestines, liver, and kidney was investigated by immunohistochemical method. CYP epoxygenases are expressed already in early stages of development in these embryonic/fetal tissues (as early as 7th week of IUD in the intestines, 5th week of IUD in the liver, and 6th week of IUD in the kidney). In kidney, CYP epoxygenases are expressed in the metanephrogenic blastema (but not in the uninduced mesenchyme) and in the tubular system. In the intestines, diverse CYP epoxygenases distribution along crypt-villus axis could suggest role in cell differentiation. Moreover, we detected higher CYP2J2 level in these organs than in adult tissue samples.
- Klíčová slova
- CYP epoxygenases, human embryos, intestine, kidney, liver,
- MeSH
- časové faktory MeSH
- cytochrom P-450 CYP2J2 MeSH
- cytochrom P450 CYP2C8 genetika MeSH
- embryo savčí enzymologie MeSH
- imunohistochemie MeSH
- játra embryologie enzymologie MeSH
- ledviny embryologie enzymologie MeSH
- lidé embryologie MeSH
- střeva embryologie enzymologie MeSH
- systém (enzymů) cytochromů P-450 genetika metabolismus MeSH
- vývojová regulace genové exprese * MeSH
- Check Tag
- lidé embryologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CYP2J2 protein, human MeSH Prohlížeč
- cytochrom P-450 CYP2J2 MeSH
- cytochrom P450 CYP2C8 MeSH
- systém (enzymů) cytochromů P-450 MeSH
Adult B-lymphopoiesis is suppressed by the inhibitory effects of elevated estrogens during pregnancy. At the same time, hematopoietic cells in the fetal liver are resistant to this suppression by estrogens and ensure active production of B-cells. We investigated whether this unresponsiveness to estrogens of fetal cells also applies to cells obtained from a newborn liver and projects into the adult hematopoiesis when fetal liver cells are transplanted to adult mice. Mixtures of fetal liver (E14.5), neonatal liver (P0.5) and adult bone marrow (BM) cells were co-transplanted into adult primary and secondary recipients treated with high doses of estrogen in the Ly5.1/Ly5.2 congenic mouse model. Total chimerism as a proportion of all nucleated blood cells, chimerism as a proportion of B220+ B-cells, and of other blood cell lineages as well, were determined by flow cytometry. B-lymphopoiesis derived from fetal liver (E14.5) stem cells remained resistant to estrogen after transplantation into both primary and secondary adult recipients, for up to 280 days. In contrast, B-lymphopoiesis derived from neonatal liver (P0.5) stem cells was resistant to estrogen only for approximately 50 days after the primary transplantation to the adult BM microenvironment. These results provide further evidence for a critical developmental period of B-lymphopoiesis during its fetal liver stage. In the mouse, critical developmental events that allow for the subsequent expressed sensitivity of B-lymphopoiesis for suppression by estrogens after sexual maturation appear to occur during the period of late-stage fetal liver hematopoiesis before its migration to the bone marrow.
- MeSH
- B-lymfocyty cytologie imunologie MeSH
- estradiol farmakologie MeSH
- hematopoetické kmenové buňky cytologie imunologie MeSH
- játra embryologie MeSH
- lymfopoéza imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- novorozená zvířata MeSH
- průtoková cytometrie MeSH
- těhotenství MeSH
- transplantace hematopoetických kmenových buněk metody MeSH
- vývoj plodu imunologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- estradiol MeSH
Three ABC transporters (MDR1, MRP1, BCRP), belonging to the family of multidrug resistance (MDR) proteins, play a crucial role in the protection mechanisms during embryogenesis and mediate drug resistance in cancer cells. The distribution of these transporters in the series of human embryonal/fetal intestine, liver and kidneys of various stages of intrauterine development (IUD) by indirect two-step immunohistochemical method was investigated. The organ- and age-specific expression patterns of these transporters were depicted and compared with the expression in adult organs. The evaluation of intestine and liver samples demonstrate differences in expression pattern of ABC transporters during IUD. On the contrary, in kidneys the age-specific localization was not observed. However, the increasing positivity from the kidney surface towards deeper, more differentiated parts was found. Hopefully, our study may contribute to elucidation of the role of multidrug resistance (MDR) pathways during IUD in man.
- MeSH
- ABC transportéry biosyntéza genetika metabolismus MeSH
- embryonální vývoj genetika fyziologie MeSH
- exprese genu MeSH
- játra embryologie MeSH
- ledviny embryologie MeSH
- lidé MeSH
- mnohočetná léková rezistence MeSH
- P-glykoproteiny biosyntéza genetika metabolismus MeSH
- střeva embryologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportéry MeSH
- P-glykoproteiny MeSH
