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Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases.
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Pulpa Dental , Medicina Regenerativa , Células Madre , Humanos , Pulpa Dental/citología , Medicina Regenerativa/métodos , Células Madre/citología , Células Madre/metabolismo , Animales , Diferenciación Celular , Trasplante de Células Madre/métodos , ARN no Traducido/genéticaRESUMEN
OBJECTIVES: Group B streptococcus (GBS) colonization among pregnant women is the leading cause of neonatal infection. Intrapartum antibiotic prophylaxis (IAP) is the most effective method to reduce the incidents of neonatal sepsis. We describe compliance with GBS management and the implementation of IAP in the context of the long-term effect of antibiotics. MATERIAL AND METHODS: The study was conducted among 249 childbearing women hospitalized between January 2022 and February 2022 at University Clinical Center in Gdansk, Poland. The data were obtained from the questionnaire and medical records. We analyzed maternal colonization with GBS, compliance with GBS screening and treatment guidelines, risk factors contributing to GBS colonization, IAP administration, and neonatal congenital infection occurrence. RESULTS: Of all patients, 240 (96.4%) were screened for GBS, 215 (89.6%) between 35-37 weeks of gestation. Fifty (20%) were GBS-positive, 184 (74%) negative, 15 (6%) had unknown GBS status. There were no significant differences between the GBS-positive and GBS-negative groups in maternal age, mode of delivery, gestational age at birth, maternal comorbidities, parity, GBS status in previous pregnancies, and the development of infection among infants of both groups, regardless of IAP administration. Of all the studied women, 158 (63.5%) received antibiotics, 91 (36.5%) did not. The study showed the low positive and the high negative predictive value of the antenatal GBS screening test. CONCLUSIONS: We found that compliance with the universal GBS screening is widespread. The management of women with absent or only partial screening test requires assessing the risk factors before administering IAP.
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Antibacterianos , Profilaxis Antibiótica , Complicaciones Infecciosas del Embarazo , Infecciones Estreptocócicas , Streptococcus agalactiae , Humanos , Femenino , Embarazo , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/prevención & control , Profilaxis Antibiótica/estadística & datos numéricos , Adulto , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/epidemiología , Polonia , Recién Nacido , Antibacterianos/uso terapéutico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Factores de Riesgo , Trabajo de PartoRESUMEN
OBJECTIVES: The Polish criteria for "intrauterine death" include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. MATERIAL AND METHODS: An analysis using 142,662 births in the period between 2015-2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. RESULTS: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. CONCLUSIONS: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often.
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Introduction: Preeclampsia is responsible for more than 70 000 and 500 000 maternal and fetal deaths, respectively each year. Incomplete remodelling of the spiral arteries in placenta is the most accepted theory of preeclampsia pathogenesis. However, the process is complexed with immunological background, as pregnancy resembles allograft transplantation. Fetus expresses human leukocyte antigens (HLA) inherited from both parents, thus is semiallogeneic to the maternal immune system. Therefore, induction of fetal tolerance is crucial for physiological outcome of pregnancy. Noteworthy, the immunogenicity of discordant HLA antigens is determined by functional epitopes called eplets, which are continuous and discontinuous short sequences of amino acids. This way various HLA molecules may express the same eplet and some HLA incompatibilities can be more immunogenic due to different eplet combination. Therefore, we hypothesized that maternal- fetal HLA incompatibility may be involved in the pathogenesis of gestational hypertension and its progression to preeclampsia. We also aimed to test if particular maternal-fetal eplet mismatches are more prone for induction of anti- fetal HLA antibodies in gestational hypertension and preeclampsia. Methods: High resolution next-generation sequencing of HLA-A, -B, -C, -DQB1 and -DRB1 antigens was performed in mothers and children from physiological pregnancies (12 pairs) and from pregnancies complicated with gestational hypertension (22 pairs) and preeclampsia (27 pairs). In the next step HLA eplet identification and analysis of HLA eplet incompatibilities was performed with in silico approach HLAMatchmaker algorithm. Simultaneously maternal sera were screened for anti-fetal HLA class I, class II and anti-MICA antibodies with Luminex, and data were analyzed with HLA-Fusion software. Results: We observed that high HLA-C, -B, and DQB1 maternal-fetal eplet compatibility was associated with severe preeclampsia (PE) manifestation. Both quantity and quality of HLA epletmismatches affected the severity of PE. Mismatches in HLA-B eplets: 65QIA+76ESN, 70IAO, 180E, HLA-C eplets: 193PL3, 267QE, and HLA-DRB1 eplet: 16Y were associated with a mild outcome of preeclampsia if the complication occurred. Conclusions: High HLA-C, HLA-DQB1 and HLA-B eplet compatibility between mother and child is associated with severe manifestation of preeclampsia. Both quantity and quality of maternal-fetal HLA eplet mismatches affects severity of preeclampsia.
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Hipertensión Inducida en el Embarazo , Preeclampsia , Embarazo , Femenino , Niño , Humanos , Antígenos HLA-C , Antígenos HLA , Feto , Antígenos HLA-BRESUMEN
BACKGROUND: Breast milk is an exceptional source of nutrients for neonates, delivering a unique composition of bioactive ingredients such as immunoglobulins, hormones and oligosaccharides. Our research aimed to understand the attitude of medical staff towards milk donation and its use in the NICU (Neonatal Intensive Care Unit) and to determine the influence the milk bank has had on the feeding practices of our patients after the introduction of local Human Milk Bank (HMB). METHODS: Twelve closed-question questionnaires were distributed among employees from the Department of Neonatology and Obstetrics before and after (identical set of questions) the implementation of the HMB. The attitudes of staff towards different aspect of milk banking were recorded. RESULTS: We obtained 67 fully answered questionnaires in 2019 and 48 questionnaires in 2021. After comparing the responses, the analysis of how staff's attitudes have changed was performed. As a second step, four hundred sixty-eight neonates born consecutively in December 2018 (N.=171) and then in December 2019 (N.=297), before and after the HMB introduction, respectively, participated in the study at the Medical University of Gdansk, Poland. Patients' medical charts were retrospectively analyzed. Since the assemblage of the HMB, there has been a significant improvement in the staff's attitude towards the use of donor milk (DM) (68.7% before, 93.8% after HMB) and its safety (65.7% before, 97.9% after HMB). There was also a significant increment in feeding newborns using breast milk compared to formula milk. CONCLUSIONS: HMB allows for the collection of donor milk, matching mother's-own-milk by gestational age and stage of lactation, ensuring adequate composition for the targeted nutritional requirements of premature infants. These findings support the relevance of our study, highlighting the importance and benefits of expanding HMB worldwide and increasing education for mothers and medical staff regarding donor milk.
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Wharton's jelly (WJ) contains mesenchymal stem cells (MSCs) exhibiting broad immunomodulatory properties and differentiation capacity, which makes them a promising tool for cellular therapies. Although the osteogenic, chondrogenic and adipogenic differentiation is a gold standard for proper identification of MSCs, it is important to elucidate the exact molecular mechanisms governing these processes to develop safe and efficient cellular therapies. Umbilical cords were collected from healthy, full-term deliveries, for subsequent MSCs (WJ-MSCs) isolation. WJ-MSCs were cultivated in vitro for osteogenic, chondrogenic, adipogenic and neurogenic differentiation. The RNA samples were isolated and the transcript levels were evaluated using NovaSeq platform, which led to the identification of differentially expressed genes. Expression of H19 and SLPI was enhanced in adipocytes, chondrocytes and osteoblasts, and NPPB was decreased in all analyzed groups compared to the control. KISS1 was down-regulated in adipocytes, chondrocytes, and neural-like cells compared to the control. The most of identified genes were already implicated in differentiation of MSCs; however, some genes (PROK1, OCA2) have not yet been associated with initiating final cell fate. The current results indicate that both osteo- and adipo-induced WJ-MSCs share many similarities regarding the most overexpressed genes, while the neuro-induced WJ-MSCs are quite distinctive from the other three groups. Overall, this study provides an insight into the transcriptomic changes occurring during the differentiation of WJ-MSCs and enables the identification of novel markers involved in this process, which may serve as a reference for further research exploring the role of these genes in physiology of WJ-MSCs and in regenerative medicine.
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Hormonas Gastrointestinales , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina , Gelatina de Wharton , Humanos , Condrocitos , Adipocitos , Diferenciación Celular/genética , Osteoblastos , Factores InmunológicosRESUMEN
During pregnancy, the placenta undergoes a natural aging process, which is considered normal. However, it has been hypothesized that an abnormally accelerated and premature aging of the placenta may contribute to placenta-related health issues. Placental senescence has been linked to several obstetric complications, including abnormal fetal growth, preeclampsia, preterm birth, and stillbirth, with stillbirth being the most challenging. A systematic search was conducted on Pubmed, Embase, and Scopus databases. Twenty-two full-text articles were identified for the final synthesis. Of these, 15 presented original research and 7 presented narrative reviews. There is a paucity of evidence in the literature on the role of placental aging in late small for gestational age (SGA), fetal growth restriction (FGR), and stillbirth. For future research, guidelines for both planning and reporting research must be implemented. The inclusion criteria should include clear differentiation between early and late SGA and FGR. As for stillbirths, only those with no other known cause of stillbirth should be included in the studies. This means excluding stillbirths due to congenital defects, infections, placental abruption, and maternal conditions affecting feto-maternal hemodynamics.
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Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exhibit multilineage differentiation potential, adhere to plastic, and express a specific set of surface markers-CD105, CD73, CD90. Although there are relatively well-established differentiation protocols for WJ-MSCs, the exact molecular mechanisms involved in their in vitro long-term culture and differentiation remain to be elucidated. In this study, the cells were isolated from Wharton's jelly of umbilical cords obtained from healthy full-term deliveries, cultivated in vitro, and differentiated towards osteogenic, chondrogenic, adipogenic and neurogenic lineages. RNA samples were isolated after the differentiation regimen and analyzed using an RNA sequencing (RNAseq) assay, which led to the identification of differentially expressed genes belonging to apoptosis-related ontological groups. ZBTB16 and FOXO1 were upregulated in all differentiated groups as compared to controls, while TGFA was downregulated in all groups. In addition, several possible novel marker genes associated with the differentiation of WJ-MSCs were identified (e.g., SEPTIN4, ITPR1, CNR1, BEX2, CD14, EDNRB). The results of this study provide an insight into the molecular mechanisms involved in the long-term culture in vitro and four-lineage differentiation of WJ-MSCs, which is crucial to utilize WJ-MSCs in regenerative medicine.
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Células Madre Mesenquimatosas , Gelatina de Wharton , Humanos , Transcriptoma , Condrocitos , Diferenciación Celular/genética , Adipocitos , Apoptosis/genética , Osteoblastos , Células Cultivadas , Proteínas del Tejido NerviosoRESUMEN
Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40-160 nm in diameter, produced by most mammalian cells in both physiological and pathological conditions. Exosomes are formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell communication. In terms of cancer, exosomes play important roles as mediators of intercellular communication, leading to tumor progression. Moreover, they can serve as biomarkers for cancer detection and progression. Therefore, their utilization in cancer therapies has been suggested, either as drug delivery carriers or as a diagnostic tool. However, exosomes were also reported to be involved in cancer drug resistance via transferring information of drug resistance to sensitive cells. It is important to consider the current knowledge regarding the role of exosomes in cancer, drug resistance, cancer therapies, and their clinical application in cancer therapies.
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Exosomas , Neoplasias , Animales , Humanos , Exosomas/fisiología , Neoplasias/patología , Portadores de Fármacos/uso terapéutico , Sistemas de Liberación de Medicamentos , Carcinogénesis , MamíferosRESUMEN
Respiratory complications are among the most common problems addressed in neonatology in the first hours after birth, whereas the risk of any cancer in the neonatal period is 28 per million. Sarcomas, malignant mesenchymal neoplasms, account for about 8% of all neoplasms in the neonatal period. We report on a male neonate born at 36 + 4/7 weeks of gestation, diagnosed with retropharyngeal synovial carcinoma. Ineffective respiratory movements and generalized cyanosis were the first symptoms to be noted. On the ultrasound examination of the neck, a tumor of the retropharyngeal space was exposed, then visualized by an MRI of the head and neck. The biopsy analysis revealed the diagnosis of an extremely rare tumor in a neonate. The location of its growth was atypical, contributing to a diagnostic challenge. The neoplasm was treated solely with chemotherapy concordantly with the CWS protocol, individually customized for our patient. Preterm birth, as in our case, 36 + 4/7 weeks of gestation, may imply a possible need for resuscitation or support in the transition period. Aggressive high-grade tumors of the head and neck region are locally invasive and prone to metastasize. However, prognosis in infants is hard to estimate, therefore both individualized treatment and multidisciplinary care should be tailored to the needs of the patient.
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Hypothesis: The activity of natural killer (NK) cells is considered an important factor for the tolerance of the fetus during pregnancy. The complications of pregnancy, such as hypertensive disorders (HDP), may be therefore associated with this immune compartment. Methods: The current study included 41 pregnant women diagnosed with HDPs (Gestational Hypertension; GH or Preeclampsia; PE) and 21 healthy women. All the patients were under continuous obstetric care during the pregnancy and labour. The number of mother-child mismatches within killer immunoglobulin-like receptors (KIRs), their ligands [MM], and missing KIR ligands [MSLs] was assessed. KIRs and their ligands were assessed with Next Generation Sequencing (NGS) and Polymerase Chain Reaction Sequence-Specific Oligonucleotide (PCR-SSO) typing. The subsets of NK cells were assessed with multicolor flow cytometry and correlated to the number of MSLs. Results: The number of MSLs was significantly higher in HDP patients when compared to healthy non-complicated pregnancy patients. Some MSLs, such as those with 2DS2 activating KIR, were present only in HDP patients. The percentage of CD56+CD16-CD94+ NK cells and CD56+CD16-CD279+ NK cells correlated with the number of MSLs with inhibiting KIRs only in healthy patients. In HDP patients, there was a correlation between the percentage of CD56-CD16+CD69+ NK cells and the number of MSLs with inhibiting and activating KIRs. As compared to the healthy group, the percentage of CD56+CD16-CD279+ NK cells and CD56-CD16+CD279+ NK cells were lower in HDP patients. HDP patients were also characterized by a higher percentage of CD56+CD16+perforin+ NK cells than their healthy counterparts. Conclusions: Patients with HDP were characterized by a higher number of MSLs within the KIRs receptors. It seemed that the number of MSLs in the healthy group was balanced by various receptors, such as CD94 or inhibitory CD279, expressed on NK cells. Conversely, in HDP patients the number of MSLs was associated with the activation detected as the increased level of CD69+ NK cells.
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Hipertensión Inducida en el Embarazo , Receptores KIR , Femenino , Humanos , Hipertensión Inducida en el Embarazo/metabolismo , Células Asesinas Naturales/metabolismo , Ligandos , Perforina/metabolismo , Receptores KIR/metabolismoRESUMEN
Human gestation leads to a number of physiological alterations which peak at the development of placentta known for, among many other functions, being a transient but highly potent endocrine organ. Hormonal activity of placenta is marked by its ability to continuously produce and secrete high levels of progesterone. Progesterone guards the well-being of the fetoplacental unit throughout the gestation and one of the proposed mechanisms of this principle involves the development of local and systemic immune tolerance mainly due to impediment of CD4+ lymphocyte activation. However, though these alterations are present and well-established, autoimmunity is not entirely rare and a wide spectrum of diseases can continue, or develop de novo, throughout the gestation or even after the delivery. Up-to-date data supports the existence of a relationship between the clinical course of chosen autoimmune diseases and levels of circulating sex steroids. The most common autoimmune endocrinopathies in pregnant women are Hashimoto's disease, Graves' disease, and, more rarely, primary adrenal insufficiency in the form of Addison's disease. Gestation can influence the clinical course of these endocrinopathies in patients who were diagnosed before conception. Multiple particles, like TSH-receptor stimulating antibodies, thyroid hormones, glucocorticoids, and anti-thyroid medications, can cross the placental barrier and evoke biological action in fetal tissues. Thyroid pathology in the form of postpartum thyroiditis is particularly prevalent in patients with positive anti-thyroperoxidase and anti-thyroglobulin antibodies. Certain populations are more at risk of developing numerous gestational complications and require regular follow-up. In our paper, we would like to address physiological, physiopathological, and clinical aspects of endocrine autoimmunity throughout human gestation, as well as special circumstances to consider in pregnant women.
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Enfermedades Autoinmunes , Enfermedad de Graves , Enfermedades Autoinmunes/complicaciones , Autoinmunidad , Femenino , Humanos , Placenta , Embarazo , ProgesteronaRESUMEN
Modern science is becoming increasingly committed to environmentally friendly solutions, mitigating the impact of the developing human civilisation on the environment. One of the leading fields aimed at sustainable agriculture is in vitro meat production. Cellular agriculture aims to provide a source of animal-free meat products, which would decrease worldwide nutritional dependency on animal husbandry, thereby reducing the significant impact of this industry on Earth's climate. However, while some studies successfully produced lab-based meat on a small scale, scalability of this approach requires significant optimisation of the methodology in order to ensure its viability on an industrial scale. One of the methodological promises of in vitro meat production is the application of cell suspension-based bioreactors. Hence, this study focused on a complex transcriptomic comparison of adherent undifferentiated, differentiated and suspension-cultured myosatellite cells, aiming to determine the effects of different culture methods on their transcriptome. Modern next-generation sequencing (RNAseq) was used to determine the levels of transcripts in the cultures' cell samples. Then, differential expression and pathway analyses were performed using bionformatical methods. The significantly regulated pathways included: EIF2, mTOR, GP6, integrin and HIFα signalling. Differential regulation of gene expression, as well as significant enrichment and modulation of pathway activity, suggest that suspension culture potentially promotes the ex vivo-associated loss of physiological characteristics and gain of plasticity. Therefore, it seems that suspension cultures, often considered the desired method for in vitro meat production, require further investigation to fully elucidate their effect on myosatellite cells and, therefore, possibly enable their easier scalability to ensure suitability for industrial application.
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Técnicas de Cultivo de Célula , Mioblastos , Animales , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular/genética , Ontología de Genes , Transducción de Señal/genéticaRESUMEN
Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.
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Diferenciación Celular/genética , Linaje de la Célula/genética , Células Madre Mesenquimatosas/citología , Medicina Regenerativa , Líquido Amniótico/citología , Autorrenovación de las Células/genética , Células Madre Embrionarias/citología , Células Madre Embrionarias/trasplante , Femenino , Humanos , Trasplante de Células Madre Mesenquimatosas , Placenta/citología , Placenta/trasplante , Embarazo , Cordón Umbilical/citología , Cordón Umbilical/trasplanteRESUMEN
Obesity is a known factor in the development of preeclampsia. This paper links adipose tissue pathologies with aberrant placental development and the resulting preeclampsia. PPARγ, a transcription factor from the ligand-activated nuclear hormone receptor family, appears to be one common aspect of both pathologies. It is the master regulator of adipogenesis in humans. At the same time, its aberrantly low activity has been observed in placental pathologies. Overweight and obesity are very serious health problems worldwide. They have negative effects on the overall mortality rate. Very importantly, they are also conducive to diseases linked to impaired placental development, including preeclampsia. More and more people in Europe are suffering from overweight (35.2%) and obesity (16%) (EUROSTAT 2021 data), some of them young women planning pregnancy. As a result, we will be increasingly encountering obese pregnant women with a considerable risk of placental development disorders, including preeclampsia. An appreciation of the mechanisms shared by these two conditions may assist in their prevention and treatment. Clearly, it should not be forgotten that health education concerning the need for a proper diet and physical activity is of utmost importance here.
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Obesidad/fisiopatología , PPAR gamma/metabolismo , Enfermedades Placentarias/fisiopatología , Preeclampsia/patología , Femenino , Humanos , Preeclampsia/etiología , Preeclampsia/metabolismo , EmbarazoRESUMEN
OBJECTIVE: To develop a multifactorial model that allows the prediction of bronchopulmonary dysplasia (BPD) in preterm newborns. MATERIALS AND METHODS: A single-center retrospective study of infants born below 32 + 0 weeks gestational age. We created a receiver operating characteristic curve to assess the multifactorial BPD risk and calculate the BPD risk accuracy using the area under the curve (AUC). BPD risk was categorized using a multifactorial predictive model based on the weight of the evidence. RESULTS: Of the 278 analyzed preterm newborns, 127 (46%) developed BPD. The significant risk factors for BPD in the multivariate analysis were gestational age, number of red blood cell concentrate transfusions, number of surfactant administrations, and hemodynamically significant patent ductus arteriosus. The combination of these factors determined the risk of developing BPD, with an AUC value of 0.932. A multifactorial predictive model based on these factors, weighted by their odds ratios, identified four categories of newborns with mean BPD risks of 9%, 59%, 82%, and 100%. CONCLUSION: A multifactorial model based on easily available clinical factors can predict BPD risk in preterm newborns and inform potential preventive measures.
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Despite the increasing development of medicine, ovarian cancer is still a high-risk, metastatic disease that is often diagnosed at a late stage. In addition, difficulties in its treatment are associated with high resistance to chemotherapy and frequent relapse. Cancer stem cells (CSCs), recently attracting significant scientific interest, are considered to be responsible for the malignant features of tumors. CSCs, as the driving force behind tumor development, generate new cells by modifying different signaling pathways. Moreover, investigations on different types of tumors have shown that signaling pathways are key to epithelial-mesenchymal transition (EMT) regulation, metastasis, and self-renewal of CSCs. Based on these established issues, new therapies are being investigated based on the use of inhibitors to block CSC growth and proliferation signals. Many reports indicate that CSC markers play a key role in cancer metastasis, with hopes placed in their targeting to block this process and eliminate relapses. Current histological classification of ovarian tumors, their epidemiology, and the most recent knowledge of ovarian CSCs, with particular emphasis on their molecular background, are important aspects for consideration. Furthermore, the importance of signaling pathways involved in tumor growth, development, and metastasis, is also presented.
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Natural killer (NK) cells are part of the cellular immune response. They target mainly cancer and virally infected cells. To a high extent cytotoxic activity of NK cells is regulated inter alia by signals from killer immunoglobulin-like receptors (KIR). The major histocompatibility complex (MHC) class I molecules are important ligands for KIR receptors. Binding of ligands (such as MHC I) to the KIR receptors has the important role in solid organ or hematopoietic cell transplantation. Of note, the understanding of the relationship between KIR and MHC receptors may contribute to the improvement of transplant results. Donor-recipient matching, which also includes the KIR typing, may improve monitoring, individualize the treatment and allow for predicting possible effects after transplantation, such as the graft-versus-leukemia effect (GvL) or viral re-infection. There are also less evident implications of KIR/MHC matching, such as with pregnancy and cancer. In this review, we present the most relevant literature reports on the importance of the KIR/MHC relationship on NK cell activity and hematopoietic stem cell transplantation (HSCT)/solid organ transplantation (SOT) effects, the risk of allograft rejection, protection against post-transplant cytomegalovirus (CMV) infection, pregnancy complications, cancer and adoptive therapy with NK cells.
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Antígenos HLA/metabolismo , Trasplante de Células Madre Hematopoyéticas , Células Asesinas Naturales/inmunología , Receptores KIR/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Donantes de Tejidos , Trasplante Homólogo/métodosRESUMEN
The hallmark of preeclampsia (PE) is a shift toward persistent inflammatory response, accompanied by endothelial dysfunction. The driving forces in PE are proinflammatory cytokine and growth factors, in parallel with reduced functionality of anti-inflammatory effectors, like regulatory T cells are observed. Unfortunately, no conclusive mechanism underlying preeclampsia has been identified. For this reason, research on preeclampsia is needed to provide a state of the art understanding of the pathophysiology, identification of new diagnostics tools and the development of targeted therapies. The 68 patients were divided into three groups: gestational hypertension (GH) group (n = 19) and PE group (n = 28) and a control group (n = 21). We have tested a set of 53 cytokines, chemokines and growth factors in preeclampsia and gestational hypertension, and then compared them with normal pregnancies. Using a diagnostic test assessment characteristic parameters (IL-22, MDC/CCL22, IL-2/IL-4 ratio) have been identified and cut-off values have been proposed to diagnose preeclampsia. All parameters had high negative or positive predictive values, above 80%. In conclusion, we have proposed a potential set of immune parameters to diagnose preeclampsia.