Implications of SCFAs on the Parameters of the Lipid and Hepatic Profile in Pregnant Women.

Short-chain fatty acids (SCFAs) are the product of the anaerobic intestinal bacterial fermentation of dietary fiber and resistant starch. An abnormal intestinal microbiota may cause a reduction in the production of SCFAs, which stimulate the development of intestinal epithelial cells, nourish enterocytes, influence their maturation and proper differentiation, reduce the pH, and are an additional source of energy for the host. There have been reports of the special role of SCFAs in the regulation of glucose and lipid metabolism during pregnancy. AIM: The aim of the study was to analyze the correlation of SCFAs with lipid and hepatic metabolism during pregnancy in relation to the body weight of pregnant women. MATERIAL AND METHODS: This study was conducted in pregnant women divided into two groups: Obese (OW-overweight and obese women; n = 48) and lean (CG-control group; n = 48) individuals. The biochemical plasma parameters of lipid metabolism (TG, CH, LDL, HDL), inflammation (CRP), and liver function (ALT, AST, GGT) were determined in all of the subjects. SCFA analysis was performed in the stool samples to measure acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0 i), butyric acid (C 4:0 n), isovaleric acid (C 5:0 i) valeric acid (C 5:0 n), isocaproic acid (C 6:0 i), caproic acid (C 6:0 n), and heptanoic acid (C 7:0). RESULTS: Statistically significant differences in the concentrations of C 3:0 and C 6:0 n were found between women in the OW group compared to the CG group. The other SCFAs tested did not differ significantly depending on BMI. The C 2:0, C 3:0, and C 4:0 n ratios showed differences in both OW and CG groups. In the OW group, no relationship was observed between the concentrations of the SCFAs tested and CRP, ALT, AST. A surprising positive relationship between C 5:0 n and all fractions of the tested lipids and branched C 5:0 with CHL, HDL, and LDL was demonstrated. In the OW group, HDL showed a positive correlation with C 3:0. However, lower GGT concentrations were accompanied by higher C 4:0 and C 5:0 values, and this tendency was statistically significant. CONCLUSIONS: The results of our research show that some SCFAs are associated with hepatic lipid metabolism and CRP concentrations, which may vary with gestational weight. Obesity in pregnancy reduces the amount of SCFAs in the stool, and a decrease in the level of butyrate reduces liver function.

Short-Chain Fatty Acids, Maternal Microbiota and Metabolism in Pregnancy.

Short-chain fatty acids (SCFAs), as products of intestinal bacterial metabolism, are particularly relevant in the diagnosis of intestinal dysbiosis. The most common studies of microbiome metabolites include butyric acid, propionic acid and acetic acid, which occur in varying proportions depending on diet, age, coexisting disease and other factors. During pregnancy, metabolic changes related to the protection of energy homeostasis are of fundamental importance for the developing fetus, its future metabolic fate and the mother's health. SCFAs act as signaling molecules that regulate the body's energy balance through G-protein receptors. GPR41 receptors affect metabolism through the microflora, while GPR43 receptors are recognized as a molecular link between diet, microflora, gastrointestinal tract, immunity and the inflammatory response. The possible mechanism by which the gut microflora may contribute to fat storage, as well as the occurrence of gestational insulin resistance, is blocking the expression of the fasting-induced adipose factor. SCFAs, in particular propionic acid via GPR, determine the development and metabolic programming of the fetus in pregnant women. The mechanisms regulating lipid metabolism during pregnancy are similar to those found in obese people and those with impaired microbiome and its metabolites. The implications of SCFAs and metabolic disorders during pregnancy are therefore critical to maternal health and neonatal development. In this review paper, we summarize the current knowledge about SCFAs, their potential impact and possible mechanisms of action in relation to maternal metabolism during pregnancy. Therefore, they constitute a contemporary challenge to practical nutritional therapy. Material and methods: The PubMed database were searched for "pregnancy", "lipids", "SCFA" in conjunction with "diabetes", "hypertension", and "microbiota", and searches were limited to work published for a period not exceeding 20 years in the past. Out of 2927 publication items, 2778 papers were excluded from the analysis, due to being unrelated to the main topic, conference summaries and/or articles written in a language other than English, while the remaining 126 publications were included in the analysis.

The possible role of corticosterone in regulating sodium and potassium concentrations in human milk.

OBJECTIVES: The aim of the study was to find the presence of corticosterone as a regular human milk constituent. We have evaluated the correlation of concentrations between the analyzed hormone and sodium and potassium in breast milk and serum. MATERIAL AND METHODS: Hand expressing breast milk samples and median cubital vein blood samples had been taken from 69 healthy, lactating women in early puerperium period (between the 3rd and 10th day) twice, before and after breastfeeding. Corticosterone concentrations in human plasma and breast milk were determined by radioimmunoassayed method. Direct assays were performed before and after breastfeeding, twice. The serum and milk sodium and potassium concentrations were estimated by Flame Emission analyzer CIBA-Corning 480, equipped with an automatic diluter. RESULTS: Corticosterone was found in all milk samples, which is an original observation, and its concentration in milk was a few times lower than in serum. Its concentration values in human serum when were not higher than 3 nmol/L (n = 108) positively correlated with its concentrations in milk, and those exceeding 3 nmol/L (n = 30) have demonstrated a negative correlation. An original finding has shown a positive correlation between concentrations of corticosterone in human serum and of potassium in human milk (r = 0.018, p < 0.03). An attempt was also made to determine the presence of aldosterone in breast milk, but the radioimmunoassay did not reveal its presence. CONCLUSIONS: The results confirm a relation between potassium concentration in milk and serum corticosterone concentration delivered to mammal gland with blood.

The Role of Arachidonic and Linoleic Acid Derivatives in Pathological Pregnancies and the Human Reproduction Process.

The aim of the available literature review was to focus on the role of the proinflammatory mediators of AA and LA derivatives in pathological conditions related to reproduction and pregnancy. Arachidonic (AA) and linoleic acid (LA) derivatives play important roles in human fertility and the course of pathological pregnancies. Recent studies have demonstrated that uncontrolled inflammation has a significant impact on reproduction, spermatogenesis, endometriosis, polycystic ovary syndrome (PCOS) genesis, implantation, pregnancy and labor. In addition, cyclooxygenase-mediated prostaglandins and AA metabolite levels are higher in women's ovarian tissue when suffering from PCOS. It has been demonstrated that abnormal cyclooxygenase-2 (COX-2) levels are associated with ovulation failure, infertility, and implantation disorders and the increase in 9-HODE/13-HODE was a feature recognized in PCOS patients. Maintaining inflammation without neutrophil participation allows pregnant women to tolerate the fetus, while excessive inflammatory activation may lead to miscarriages and other pathological complications in pregnancies. Additionally AA and LA derivatives play an important role in pregnancy pathologies, e.g., gestational diabetes mellitus, preeclampsia (PE), and fetal growth, among others. The pathogenesis of PE and other pathological states in pregnancy involving eicosanoids have not been fully identified. A significant expression of 15-LOX-1,2 was found in women with PE, leading to an increase in the synthesis of AA and LA derivatives, such as hydroxyeicozatetraenoic acids (HETE) and hydroxyoctadecadiene acids (HODE). Synthesis of the metabolites 5-, 8-, 12-, and 15-HETE increased in the placenta, while 20-HETE increased only in umbilical cord blood in women with preeclampsia compared to normal pregnancies. In obese women with gestational diabetes mellitus (GDM) an increase in epoxygenase products in the cytochrome P450 (CYP) and the level of 20-HETE associated with the occurrence of insulin resistance (IR) were found. In addition, 12- and 20-HETE levels were associated with arterial vasoconstriction and epoxyeicosatrienoic acids (EETs) with arterial vasodilatation and uterine relaxation. Furthermore, higher levels of 5- and 15-HETE were associated with premature labor. By analyzing the influence of free fatty acids (FFA) and their derivatives on male reproduction, it was found that an increase in the AA in semen reduces its amount and the ratio of omega-6 to omega-3 fatty acids showed higher values in infertile men compared to the fertile control group. There are several studies on the role of HETE/HODE in relation to male fertility. 15-Hydroperoxyeicosatetraenoic acid may affect the integrity of the membrane and sperm function. Moreover, the incubation of sperm with physiologically low levels of prostaglandins (PGE2/PGF2α) improves the functionality of human sperm. Undoubtedly, these problems are still insufficiently understood and require further research. However, HETE and HODE could serve as predictive and diagnostic biomarkers for pregnancy pathologies (especially in women with risk factors for overweight and obesity). Such knowledge may be helpful in finding new treatment strategies for infertility and the course of high-risk pregnancies.

The Associations of SCFA with Anthropometric Parameters and Carbohydrate Metabolism in Pregnant Women.

Short-chain fatty acids (SCFAs) mediate the transmission of signals between the microbiome and the immune system and are responsible for maintaining balance in the anti-inflammatory reaction. Pregnancy stages alter the gut microbiota community structure, which also synthesizes SCFAs. The study involved 90 pregnant women, divided into two groups: 48 overweight/obese pregnant women (OW) and 42 pregnant women with normal BMI (CG). The blood samples for glucose, insulin, and HBA1c were analyzed as well as stool samples for SCFA isolation (C2:0; C3:0; C4:0i; C4:0n; C5:0i; C5:0n; C6:0i; C6:0n) using gas chromatography. The SCFA profile in the analyzed groups differed significantly. A significant positive correlation between C2:0, C3:0, C4:0n and anthropometric measurements, and between C2:0, C3:0, C4:0n, and C5:0n and parameters of carbohydrate metabolism was found. SCFA levels fluctuate during pregnancy and the course of pregnancy and participate in the change in carbohydrate metabolism as well. The influence of C2:0 during pregnancy on anthropometric parameters was visible in both groups (normal weight and obese). Butyrate and propionate regulate glucose metabolism by stimulating the process of intestinal gluconeogenesis. The level of propionic acid decreases with the course of pregnancy, while its increase is characteristic of obese women, which is associated with many metabolic adaptations. Propionic and linear caproic acid levels can be an important critical point in maintaining lower anthropometric parameters during pregnancy.

Morphological estimation of incomplete uterine scar rupture (dehiscence) in post- cesarean deliveries. Immunohistochemical studies.

OBJECTIVES: No studies were found that analysed the properties of the caesarean scar, therefore the new study analysed the myometrial immunohistochemical expression of elastin, collagen type VI, alpha smooth muscle actin, smooth muscle myosin heavy chain, and endothelial cell marker CD31. The aim of the study was to determine the risk of uterine rupture in future pregnancies. MATERIAL AND METHODS: A total of 89 women of Caucasian ethnicity were eligible: 20 healthy pregnant women, who underwent repeat caesarean section complicated by incomplete uterine scar rupture before labour, and 69 healthy pregnant women, who underwent repeat caesarean section without subsequent uterine scar rupture as the control group. In all cases, uterine tissue sample from the scarred region was collected during the caesarean section operation. RESULTS: The lack of observed significant changes of elastin, collagen type VI, alpha smooth muscle actin, smooth muscle myosin heavy chain and endothelial cell marker CD31 concentrations in ruptured and unruptured uteri indicates that these components cannot be found to be a marker of risk of uterine rupture in future pregnancies. CONCLUSIONS: It could be suggested that the examined components do not contribute to the mechanism of maintaining integrity and are not responsible for the biomechanical properties of the uterine scar.

Perinatal factors affecting the gut microbiota - are they preventable?

Intestinal microbiota affects many aspects of physiological processes. The type of microbiota in the early stages of life is a critical element conditioning the development of the immune response and food tolerance. Disturbed colonization of the digestive tract resulting from the amount or diversity of bacteria colonies stimulates an inflammatory response that is associated in later life with inflammatory and autoimmune diseases. One of the elements disturbing normal colonization in the perinatal period is the operative way of delivery by caesarean section and the administration of antibiotics, used as a prophylactic measure as well as for therapeutic reasons. Based on the current state of knowledge, there is a lot of evidence demonstrating the long-term adverse effects of these modifying agents for gut microbiota, which should be kept to a minimum as far as possible.

Intrapartum PCR assay is a fast and efficient screening method for Group B Streptococcus detection in pregnancy.

OBJECTIVES: The aim of the study is to verify the usefulness of a real-time polymerase chain reaction versus the culture for ante- and intrapartum group B Streptococcus maternal colonization (GBS) and prevalence of discordance during the period between an antepartum screening and delivery. MATERIAL AND METHODS: The study involved 106 pregnant women aged 18 to 39 years. Rectovaginal samples were collected according to CDC guidelines at 35-37 weeks of gestation as well as in the first stage of labour, during physical examination and were analyzed using two independent diagnostic methods: microbiological culture with standard culture and polymerase chain reaction with real-time assay. RESULTS: The discordance between antenatal and intrapartum GBS prevalence has been demonstrated as well as differences associated with diagnostic strategies, culture and PCR. CONCLUSIONS: Intrapartum detection of GBS colonization using culture or Real-Time PCR assay as well, regardless of antenatal screening test for GBS, is very useful in identifying women who require implementation or withdrawal from prophylactic intrapartum antibiotic therapy. Real-Time PCR is a quick efficient method for GBS screening in pregnant women, which can be even applied during labor due to its short time of analyzing and high sensitivity and specificity. The above fact may indicate the need to perform the GBS test in the intrapartum period in all pregnant GBS negative women using PCR assay as a more adequate diagnostic method as the procedure could reduce the risk of a neonatal GBS infection subsequently to a prophylactic antibiotic therapy in women with an intrapartum positive GBS.

IL16 and IL18 gene polymorphisms in women with gestational diabetes.

OBJECTIVES: Gestational diabetes mellitus is a carbohydrate intolerance that occurs during pregnancy. Various inflammatory mediators are considered to be risk factors leading to GDM development. Among them are pro-inflammatory cytokines, such as IL16 and IL18. The aim of this study was to examine the association between IL16 and IL18 polymorphisms and GDM. MATERIAL AND METHODS: This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). All samples were genotyped in duplicate using allelic discrimination assays with TaqMan® probes. RESULTS: We observed that there was a decreased frequency of IL16 rs4778889 CC genotype carriers among women with GDM (CC vs. CT + TT: OR = 0.14; 95% CI = 0.02-1.15; p = 0.034). However, there was no significant difference in the distri-bution of alleles (C vs. T: OR = 0.81; 95% CI = 0.54-1.21; p = 0.30). There was a decreased frequency of the IL18 rs187238 G allele among GDM women (G vs. C: OR = 0.71; 95% CI = 0.53-0.96; p = 0.027). We also observed a decreased frequency of the IL18 rs1946518 T allele among women with GDM; however, this difference had only borderline statistical significance. We observed an association between IL18 rs187238, rs1946518 and BMI in pregnant women. CONCLUSIONS: The results of this study suggest that IL18 rs187238 and rs1946518 polymorphisms may be associated with an increased risk of GDM as well as with BMI in pregnant women.

[Outline of the history of caesarean section ­ from ancient times to the end of 17th Century].

Problems with the childbirth accompanied the human civilization since its beginning. From the ancient times, physicians and other people specializing in healing, tried to help women in this special moment of life. At the base of this exceptional meaning of childbirth for humans lies the fact, that if something is going wrong there are two victims - mother and the child. As a result, many times there had been very dramatic attempts of help in this the most difficult journey which in his life every man is undergoing. In this paper a comprehensive review of literature about the history of caesarean section from ancient times to the end of 17th century was done.

Costs of the use of carbetocin in the prevention of uterine atony following delivery of the infant by Caesarean section - retrospective multicenter study.

OBJECTIVES: The aim of this study was to compare the costs of using carbetocin in the prevention of uterine atony following delivery of the infant by Cesarean section (C-section) under epidural or spinal anesthesia with standard methods of prevention (SMP). MATERIAL AND METHODS: This retrospective multicenter study was based on data from three medical centers. A questionnaire was developed to gather patient records on consumption and costs of resources related to C-section, prevention of uterine atony and postpartum hemorrhage (PPH) treatment. Six subpopulations were considered, depending on patient characteristics. The analysis covered two perspectives: that of the hospital and of the public payer. RESULTS: The subpopulations were homogenous, which was a premise for pooling the data. The use of carbetocin in the prevention of uterine atony following Cesarean section generates savings for hospital in comparison with SMP (oxytocin) in 5 of 6 subpopulations. The biggest savings were observed amongst patients who experienced severe PPH and reached 2.6-6.2 thousand PLN per patient. Costs of services related to C-section borne by the hospitals were higher than the refund received from a public payer. The greatest underestimation reached 12.1 thousand PLN per patient. Nevertheless, loss generated by this underfunding was lower in carbetocin versus oxytocin group. CONCLUSIONS: The use of carbetocin instead of SMP gives hospitals an opportunity to make savings as well as to reduce losses resulting from the underfunding of the services provided by the National Health Fund.

The influence of BDNF on human umbilical cord blood stem/progenitor cells: implications for stem cell-based therapy of neurodegenerative disorders.

Umbilical cord blood (UCB)-derived stem/progenitor cells (SPCs) have demonstrated the potential to improve neurologic function in different experimental models. SPCs can survive after transplantation in the neural microenvironment and indu ce neuroprotection, endogenous neurogenesis by secreting a broad repertoire of trophic and immunomodulatory cytokines. In this study, the influence of brain-derived neurotrophic factor (BDNF) pre-treatment was comprehensively evaluated in a UCB-derived lineage-negative (Lin-) SPC population. UCB-derived Lin- cells were evaluated with respect to the expression of (i) neuronal markers using immunofluorescence staining and (ii) specific (TrkB) receptors for BDNF using flow cytometry. Next, after BDNF pre-treatment, Lin- cells were extensively assessed with respect to apoptosis using Western blotting and proliferation via BrdU incorporation. Furthermore, NT-3 expression levels in Lin- cells using RQ PCR and antioxidative enzyme activities were assessed. We demonstrated neuronal markers as well as TrkB expression in Lin- cells and the activation of the TrkB receptor by BDNF. BDNF pre-treatment diminished apoptosis in Lin- cells and influenced the proliferation of these cells. We observed significant changes in antioxidants as well as in the increased expression of NT-3 in Lin- cells following BDNF exposure. Complex global miRNA and mRNA profiling analyses using microarray technology and GSEA revealed the differential regulation of genes involved in the proliferation, gene expression, biosynthetic processes, translation, and protein targeting. Our results support the hypothesis that pre-treatment of stem/progenitor cells could be beneficial and may be used as an auxiliary strategy for improving the properties of SPCs.

Remifentanil for labour pain relief.

Labour is thought to be one of the most intense and painful experiences in a woman's life. Numerous studies using a Visual Analogue Scale invariably demonstrate that 20% of women in labour describe the pain as "unbearable" and 60% describe the pain as "very intense". Since the mid-1980s, continuous epidural analgesia during labour has been considered the gold standard of labour anaesthesia and is currently the most frequently used. There are situations in which this type of analgesia could not be used. An alternative pain management is administration of parenteral opioids, the most frequently used of which is pethidine. Its use is associated with adverse effects and unsatisfactory analgesia. Since the second half of the 20th century, a new generation of opioids, such as fentanyl or remifentanil, has been used. Despite their much better pharmacokinetic and pharmacodynamic parameters, obstetricians, midwives and neonatologists are most aware of pethidine, probably because it has been used for the longest period of time, despite its disadvantages and the risk that its use entails. The drug that is nearest to ideal is remifentanil. The countries in which it is widely used as an alternative type of labour anaesthesia have developed practice standards or guidelines practice. Guidelines and alternatives to pethidine protocols for effective labour analgesia in Poland might be merited.

14 Years of Polish Experience in Non-Invasive Prenatal Blood Group Diagnosis.

BACKGROUND: Blood cell antigens may cause maternal alloimmunization leading to fetal/newborn disorders. Non-invasive prenatal diagnostics (NIPD) of the blood group permits the determination of feto-maternal incompatibility. AIM: To evaluate 14 years of blood group NIPD at the Institute of Hematology and Transfusion Medicine (IHTM) in Warsaw. METHODS: Plasma DNA from 536 RhD-negative, 24 Rhc-negative, 26 RhE-negative, 43 K-negative, and 42 HPA-1a-negative pregnant women was examined by real-time PCR to detect RHD, RHCE*c, RHCE*E, RHCE*C, KEL*01 and HPA*1A, respectively. We tested for CCR5, SRY or bi-allelic polymorphisms and quantified the total or fetal DNA. RESULTS: The results of fetal antigen status prediction by NIPD in all but one case (false-positive result of KEL*01) were correct taking neonate serology as a reference. It was confirmed that all negative results of NIPD contained fetal DNA except for four cases where there was no difference between the parents' polymorphisms. CONCLUSIONS: A fetal genotype compatible with the mother was determined in 25% of all pregnancies tested at the IHTM for the fetal blood group. These cases were not at risk of disease, so it was possible to avoid invasive procedures.

Birth weight predicts the risk of gestational diabetes mellitus and pregravid obesity.

OBJECTIVES: It has been suggested that birth weight may determine metabolic abnormalities later in life. The aim of the current study was to assess the association between birth weight and future risk of gestational diabetes mellitus (GDM) and pregravid obesity in a homogenous sample of Caucasian Polish women. METHODS: In this retrospective study, we collected the medical reports of 787 women with GDM and 801 healthy pregnant women. We analyzed the following data: birth weight, age, pregravid weight, prior GDM, prior macrosomia, parity, and family history of diabetes. RESULTS: Birth weight was inversely associated with the risk of GDM; for each decrease in birth weight of 500 g, the risk increased by 11% (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.02-1.21). Birth weight was a strong predictor of GDM independent of other risk factors (OR, 1.19; 95% CI, 1.09-1.31), and it was positively correlated with pregravid weight (R = 0.21; P < 0.00001). An increase in birth weight of 500 g substantially increased the risk of overweight and obesity (OR, 1.17; 95% CI, 1.01-1.34 and OR, 1.35; 95% CI 1.11-1.64, respectively). Each of the traditional risk factors for GDM were also strong predictors of pregravid obesity: age (P < 0.0001), prior GDM (P < 0.01), prior macrosomia (P < 0.0001), multiparity (P < 0.0001), and maternal (but not paternal) history of diabetes (P < 0.0001). CONCLUSIONS: Among Caucasian Polish women, the risk of GDM is associated with low birth weight, and pregravid obesity is associated with high birth weight. Traditional risk factors for GDM, including maternal (but not paternal) history of diabetes, are also risk factors for pregravid obesity.

[Intrauterine fetal therapy of NIHF with massive pleural effusion - a case study]. / Terapia wewnatrzmaciczna plodu z obrekiem nieimmnunologicznym oraz masywnym wysiekiem oplucnowym - analiza przypadku kinicznego.

Hydrops fetalis (fetal hydrops) is a serious fetal condition defined as abnormal accumulation of fluid in two or more extravascular compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Edema is classified as immune or non-immune. Today more than 90% of fetal edema has non-immune cause. This paper presents a case of a pregnant woman who was admitted to the Obstetrics and Gynecology Department because of fetal hydrops with massive pleural effusion and polyhydramnios at 34 weeks gestation. The intrauterine therapy consisted of two treatments. During the first surgery amnioreduction, evacuation of fluid from the pleural cavity of the fetus, and shunts to both pleural cavities were performed. During the second surgery amnioreduction, cordocentesis with albumin administration and pleural shunt were performed. Intrauterine therapy led to a reduction of swelling of the fetus from 7mm up to 1-2 mm and the total evacuation of fluid from the pleural cavity and the fetal lung expansion. We also present the condition of the neonate after birth and after 12 months of life.

Humoral activity of cord blood-derived stem/progenitor cells: implications for stem cell-based adjuvant therapy of neurodegenerative disorders.

BACKGROUND: Stem/progenitor cells (SPCs) demonstrate neuro-regenerative potential that is dependent upon their humoral activity by producing various trophic factors regulating cell migration, growth, and differentiation. Herein, we compared the expression of neurotrophins (NTs) and their receptors in specific umbilical cord blood (UCB) SPC populations, including lineage-negative, CD34(+), and CD133(+) cells, with that in unsorted, nucleated cells (NCs). METHODS AND RESULTS: The expression of NTs and their receptors was detected by QRT-PCR, western blotting, and immunofluorescent staining in UCB-derived SPC populations (i.e., NCs vs. lineage-negative, CD34(+), and CD133(+) cells). To better characterize, global gene expression profiles of SPCs were determined using genome-wide RNA microarray technology. Furthermore, the intracellular production of crucial neuro-regenerative NTs (i.e., BDNF and NT-3) was assessed in NCs and lineage-negative cells after incubation for 24, 48, and 72 h in both serum and serum-free conditions. We discovered significantly higher expression of NTs and NT receptors at both the mRNA and protein level in lineage-negative, CD34(+), and CD133(+) cells than in NCs. Global gene expression analysis revealed considerably higher expression of genes associated with the production and secretion of proteins, migration, proliferation, and differentiation in lineage-negative cells than in CD34(+) or CD133(+) cell populations. Notably, after short-term incubation under serum-free conditions, lineage-negative cells and NCs produced significantly higher amounts of BDNF and NT-3 than under steady-state conditions. Finally, conditioned medium (CM) from lineage-negative SPCs exerted a beneficial impact on neural cell survival and proliferation. CONCLUSIONS: Collectively, our findings demonstrate that UCB-derived SPCs highly express NTs and their relevant receptors under steady-state conditions, NT expression is greater under stress-related conditions and that CM from SPCs favorable influence neural cell proliferation and survival. Understanding the mechanisms governing the characterization and humoral activity of subsets of SPCs may yield new therapeutic strategies that might be more effective in treating neurodegenerative disorders.

Circulating hematopoietic stem cell count is a valuable predictor of prematurity complications in preterm newborns.

BACKGROUND: The frequency of preterm labour has risen over the last few years. Hence, there is growing interest in the identification of markers that may facilitate prediction and prevention of premature birth complications. Here, we studied the association of the number of circulating stem cell populations with the incidence of complications typical of prematurity. METHODS: The study groups consisted of 90 preterm (23-36 weeks of gestational age) and 52 full-term (37-41 weeks) infants. Non-hematopoietic stem cells (non-HSCs; CD45-lin-CD184+), enriched in very small embryonic-like stem cells (VSELs), expressing pluripotent (Oct-4, Nanog), early neural (ß-III-tubulin), and oligodendrocyte lineage (Olig-1) genes as well as hematopoietic stem cells (HSCs; CD45+lin-CD184+), and circulating stem/progenitor cells (CSPCs; CD133+CD34+; CD133-CD34+) in association with characteristics of prematurity and preterm morbidity were analyzed in cord blood (CB) and peripheral blood (PB) until the sixth week after delivery. Phenotype analysis was performed using flow cytometry methods. Clonogenic assays suitable for detection of human hematopoietic progenitor cells were also applied. The quantitative parameters were compared between groups by the Mann-Whitney test and between time points by the Friedman test. Fisher's exact test was used for qualitative variables. RESULTS: We found that the number of CB non-HSCs/VSELs is inversely associated with the birth weight of preterm infants. More notably, a high number of CB HSCs is strongly associated with a lower risk of prematurity complications including intraventricular hemorrhage, respiratory distress syndrome, infections, and anemia. The number of HSCs remains stable for the first six weeks of postnatal life. Besides, the number of CSPCs in CB is significantly higher in preterm infants than in full-term neonates (p < 0.0001) and extensively decreases in preterm babies during next six weeks after birth. Finally, the growth of burst-forming unit of erythrocytes (BFU-E) and colony-forming units of granulocyte-macrophage (CFU-GM) obtained from CB of premature neonates is higher than those obtained from CB of full-term infants and strongly correlates with the number of CB-derived CSPCs. CONCLUSION: We conclude that CB HSCs are markedly associated with the development of premature birth complications. Thus, HSCs ought to be considered as the potential target for further research as they may be relevant for predicting and controlling the morbidity of premature infants. Moreover, the observed levels of non-HSCs/VSELs circulating in CB are inversely associated with the birth weight of preterm infants, suggesting non-HSCs/VSELs might be involved in the maturation of fetal organism.