RESUMO
This systematic review delves into the connections between microRNAs and preterm labor, with a focus on identifying diagnostic and prognostic markers for this crucial pregnancy complication. Covering studies disseminated from 2018 to 2023, the review integrates discoveries from diverse pregnancy-related scenarios, encompassing gestational diabetes, hypertensive disorders and pregnancy loss. Through meticulous search strategies and rigorous quality assessments, 47 relevant studies were incorporated. The synthesis highlights the transformative potential of microRNAs as valuable diagnostic tools, offering promising avenues for early intervention. Notably, specific miRNAs demonstrate robust predictive capabilities. In conclusion, this comprehensive analysis lays the foundation for subsequent research, intervention strategies and improved outcomes in the realm of preterm labor.
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MicroRNAs , Trabalho de Parto Prematuro , Humanos , Gravidez , MicroRNAs/genética , Feminino , Trabalho de Parto Prematuro/genética , Biomarcadores , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismoRESUMO
Background: Alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) are two tumor markers that are widely used in the differential diagnosis in patients with primary liver tumors. Very high levels of AFP are sporadically observed in patients with intrahepatic cholangiocarcinoma (ICC) and may cause an incorrect initial diagnosis of hepatocellular carcinoma (HCC). Methods: Two cases of tumors in cirrhotic livers were described, in which the initial diagnosis, based on very high AFP levels (Patient I: 10,464 ng/mL, Patient II: 2212 ng/mL, reference range: ≤8.04 ng/mL) was HCC. In addition, the PubMed database was searched for cases of ICC with elevated AFP. Discussion: In both individuals, liver cirrhosis was diagnosed, but there was no typical rapid "washout" in the contrast-enhanced computed tomography. Based on the histological assessment of samples obtained in the core biopsies, the initially assumed diagnosis of HCC was changed to ICC in both cases. Only nine cases of patients with ICC and high AFP levels were found in the PubMed database. The AFP levels ranged from slightly elevated to over 16,000 ng/mL. Conclusions: A very high AFP level does not necessarily correlate with the presence of HCC. Therefore, the diagnosis has to be verified histologically, when the radiological imaging is uncertain in patients with liver cirrhosis.
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Neoplasias dos Ductos Biliares , Biomarcadores Tumorais , Colangiocarcinoma , Erros de Diagnóstico , alfa-Fetoproteínas , Humanos , alfa-Fetoproteínas/análise , Colangiocarcinoma/sangue , Colangiocarcinoma/diagnóstico , Masculino , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Diagnóstico Diferencial , Idoso , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/complicações , Feminino , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND Mesenchymal stem cells (MSCs) are capable of secreting different substances, including the anti-inflammatory protein TSG-6, which can be useful in the treatment of diseases with inflammatory reactions. The main aim of this study was to evaluate the expression of the TSG-6 gene in MSCs derived from the umbilical cord. For better understanding of the anti-inflammatory properties of MSCs, we additionally assessed the expression of some interleukins (ILs). MATERIAL AND METHODS The study group included 45 patients after delivery, aged from 21 to 46 years; the average patient age was 33 years. MSCs were isolated enzymatically from umbilical cord Wharton's jelly, in vitro cultured, and characterized using flow cytometry; qPCR was performed to assess expression of the studied genes. The expression of genes of a number of pro-inflammatory ILs in MSCs was investigated in relation to the health of patients (coexistence of hypertension), the level of leukocytes, pCO2, and hemoglobin in the blood. RESULTS Our research showed that the expression of the TSG-6 gene in MSCs depends on coexisting diseases in the patient and the biochemical parameters of umbilical cord blood, including the important role of cord blood pH. We found that the levels of IL2 and IL6 expression were correlated with pCO2, and IL6 expression were correlated with pO2. CONCLUSIONS Our study suggests that maternal health status and cord blood biochemical parame-ters could affect the anti-inflammatory properties of MSCs; however, this needs to be confirmed in a future study.
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Sangue Fetal , Interleucina-6 , Humanos , Adulto , Interleucina-6/genética , Cordão Umbilical , Transporte Biológico , FamíliaRESUMO
The present study aimed to investigate the relationship between the concentrations of bisphenols residues in the amniotic fluid (AF) samples collected during amniocentesis and fetal chromosomal abnormalities in pregnant women. A total of 33 pregnant Polish women aged between 24 and 44 years, and screened to detect high risk for chromosomal defects in the first trimester, were included in this study. Samples were collected from these patients during routine diagnostic and treatment procedures at mid-gestation. The concentrations of various bisphenols residues in the samples were determined by liquid chromatography coupled with triple quadrupole tandem mass spectrometry (LC-ESI-QqQ-MS/MS). Residues of eight analytes (BPS, BPF, BPA, BPAF, BADGE, BADGEâ¢2H2O, BADGEâ¢H2Oâ¢HCl and BADGEâ¢2HCl) were detected in amniotic fluid samples in the range 0.69 ng/mL to 3.38 ng/mL. Fetuses with chromosomal abnormalities showed a slightly higher frequency of occurrence of selected bisphenols residues in the AF samples collected between 15-26 weeks of pregnancies. Finally, the proposed method was applied in the simultaneous determination of several endocrine-disrupting chemicals from bisphenol group in 33 human AF samples. BADGEâ¢H2Oâ¢HCl has been identified in the AF samples taken from women older than average in the examined group. The number of detected compounds has been significant for the following analytes: BPS, BPAF, BADGEâ¢H2Oâ¢HCl and BADGE. The proposed method may be an attractive alternative for application in large-scale human biomonitoring studies.
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Gestantes , Espectrometria de Massas em Tandem , Feminino , Humanos , Gravidez , Adulto Jovem , Adulto , Espectrometria de Massas em Tandem/métodos , Polônia , Líquido Amniótico/química , Compostos Benzidrílicos/químicaRESUMO
A comparative analysis of the placental microbiome in pregnancies with late fetal growth restriction (FGR) was performed with normal pregnancies to assess the impact of bacteria on placental development and function. The presence of microorganisms in the placenta, amniotic fluid, fetal membranes and umbilical cord blood throughout pregnancy disproves the theory of the "sterile uterus". FGR occurs when the fetus is unable to follow a biophysically determined growth path. Bacterial infections have been linked to maternal overproduction of pro-inflammatory cytokines, as well as various short- and long-term problems. Proteomics and bioinformatics studies of placental biomass allowed the development of new diagnostic options. In this study, the microbiome of normal and FGR placentas was analyzed by LC-ESI-MS/MS mass spectrometry, and the bacteria present in both placentas were identified by analysis of a set of bacterial proteins. Thirty-six pregnant Caucasian women participated in the study, including 18 women with normal pregnancy and eutrophic fetuses (EFW > 10th percentile) and 18 women with late FGR diagnosed after 32 weeks of gestation. Based on the analysis of the proteinogram, 166 bacterial proteins were detected in the material taken from the placentas in the study group. Of these, 21 proteins had an exponentially modified protein abundance index (emPAI) value of 0 and were not included in further analysis. Of the remaining 145 proteins, 52 were also present in the material from the control group. The remaining 93 proteins were present only in the material collected from the study group. Based on the proteinogram analysis, 732 bacterial proteins were detected in the material taken from the control group. Of these, 104 proteins had an emPAI value of 0 and were not included in further analysis. Of the remaining 628 proteins, 52 were also present in the material from the study group. The remaining 576 proteins were present only in the material taken from the control group. In both groups, we considered the result of ns prot ≥ 60 as the cut-off value for the agreement of the detected protein with its theoretical counterpart. Our study found significantly higher emPAI values of proteins representative of the following bacteria: Actinopolyspora erythraea, Listeria costaricensis, E. coli, Methylobacterium, Acidobacteria bacterium, Bacteroidetes bacterium, Paenisporsarcina sp., Thiodiazotropha endol oripes and Clostridiales bacterium. On the other hand, in the control group statistically more frequently, based on proteomic data, the following were found: Flavobacterial bacterium, Aureimonas sp. and Bacillus cereus. Our study showed that placental dysbiosis may be an important factor in the etiology of FGR. The presence of numerous bacterial proteins present in the control material may indicate their protective role, while the presence of bacterial proteins detected only in the material taken from the placentas of the study group may indicate their potentially pathogenic nature. This phenomenon is probably important in the development of the immune system in early life, and the placental microbiota and its metabolites may have great potential in the screening, prevention, diagnosis and treatment of FGR.
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Retardo do Crescimento Fetal , Placenta , Gravidez , Feminino , Humanos , Placenta/metabolismo , Retardo do Crescimento Fetal/patologia , Escherichia coli , Proteômica , Espectrometria de Massas em Tandem , Proteínas de Bactérias/metabolismoRESUMO
Due to their therapeutic potential, mesenchymal stem cells are the subject of intensive research on the use of their potential in the treatment of, among others, neurodegenerative diseases or immunological diseases. They are among the newest in the field of medicine. The presented study aimed to evaluate the expression of eight genes from the IAP family and the gene regulating IAP-XAF1-in stem cells derived from human milk, using the qPCR method. The relationships between the expression of genes under study and clinical data, such as maternal age, maternal BMI, week of pregnancy in which the delivery took place, bodyweight of the newborn, the number of pregnancies and deliveries, and the time elapsed since delivery, were also analyzed. The research was carried out on samples of human milk collected from 42 patients hospitalized in The Clinic of Obstetrics and Perinatology of the Independent Public Clinical Hospital No. 4, in Lublin. The conducted research confirmed the expression of the following genes in the tested material: NAIP, BIRC2, BIRC3, BIRC5, BIRC6, BIRC8, XIAP, XAF1, OCT4 and SOX2. Moreover, several dependencies of the expression of individual genes on the maternal BMI (BIRC5, XAF1 and NAIP), the time since childbirth (BIRC5, BIRC6, XAF1 and NAIP), the number of pregnancies and deliveries (BIRC2, BIRC5, BIRC6 and XAF1), the manner of delivery (XAF1 and OCT4), preterm labor (BIRC6 and NAIP) were demonstrated. Additionally, we found positive relationships between gene expression of BIRC7, BIRC8 and XAF1 and the main factors of pluripotency: SOX2 and OCT4. This work is the first to investigate the expression of genes from the IAPs family in mother's milk stem cells.
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Leite Humano , Células-Tronco , Gravidez , Feminino , Recém-Nascido , Humanos , Leite Humano/metabolismo , Células-Tronco/metabolismo , Expressão Gênica , Fator 3 de Transcrição de Octâmero/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismoRESUMO
Spinal cord injuries result in the loss of motor and sensory functions controlled by neurons located at the site of the lesion and below. We hypothesized that experimentally enhanced remyelination supports axon preservation and/or growth in the total spinal cord transection in rats. Multifocal demyelination was induced by injection of ethidium bromide (EB), either at the time of transection or twice during transection and at 5 days post-injury. We demonstrated that the number of oligodendrocyte progenitor cells (OPCs) significantly increased 14 days after demyelination. Most OPCs differentiated into mature oligodendrocytes by 60-90 dpi in double-EB-injected rats; however, most axons were remyelinated by Schwann cells. A significant number of axons passed the injury epicenter and entered the distant segments of the spinal cord in the double-EB-injected rats. Moreover, some serotoninergic fibers, not detected in control animals, grew caudally through the injury site. Behavioral tests performed at 60-90 dpi revealed significant improvement in locomotor function recovery in double-EB-injected rats, which was impaired by the blockade of serotonin receptors, confirming the important role of restored serotonergic fibers in functional recovery. Our findings indicate that enhanced remyelination per se, without substantial inhibition of glial scar formation, is an important component of spinal cord injury regeneration.
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Doenças Desmielinizantes , Remielinização , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Ratos , Animais , Axônios/patologia , Regeneração Nervosa/fisiologia , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Etídio , Doenças Desmielinizantes/patologiaRESUMO
SOX2 is a recognized pluripotent transcription factor involved in stem cell homeostasis, self-renewal and reprogramming. It belongs to, one of the SRY-related HMG-box (SOX) family of transcription factors, taking part in the regulation of embryonic development and determination of cell fate. Among other functions, SOX2 promotes proliferation, survival, invasion, metastasis, cancer stemness, and drug resistance. SOX2 interacts with other transcription factors in multiple signaling pathways to control growth and survival. The aim of the study was to determine the effect of a parturient's age, umbilical cord blood pH and length of pregnancy on the quality of stem cells derived from Wharton's jelly (WJSC) by looking at birth weight and using SOX2 gene expression as a marker. Using qPCR the authors, evaluated the expression of SOX2 in WJSC acquired from the umbilical cords of 30 women right after the delivery. The results showed a significant correlation between the birth weight and the expression of SOX2 in WJSC in relation to maternal age, umbilical cord blood pH, and the length of pregnancy. The authors observed that the younger the woman and the lower the umbilical cord blood pH, the earlier the delivery occurs, the lower the birth weight and the higher SOX2 gene expression in WJSC. In research studies and clinical applications of regenerative medicine utilizing mesenchymal stem cells derived from Wharton's Jelly of the umbilical cord, assessment of maternal and embryonic factors influencing the quality of cells is critical.
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Células-Tronco Mesenquimais , Fatores de Transcrição SOXB1 , Geleia de Wharton , Biomarcadores/metabolismo , Peso ao Nascer , Diferenciação Celular/fisiologia , Feminino , Expressão Gênica , Humanos , Recém-Nascido , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Gravidez , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Geleia de Wharton/citologia , Geleia de Wharton/metabolismoRESUMO
Coordination of four-limb movements during quadrupedal locomotion is controlled by supraspinal monoaminergic descending pathways, among which serotoninergic ones play a crucial role. Here we investigated the locomotor pattern during recovery from blockade of 5-HT7 or 5-HT2A receptors after intrathecal application of SB269970 or cyproheptadine in adult rats with chronic intrathecal cannula implanted in the lumbar spinal cord. The interlimb coordination was investigated based on electromyographic activity recorded from selected fore- and hindlimb muscles during rat locomotion on a treadmill. In the time of recovery after hindlimb transient paralysis, we noticed a presence of an unusual pattern of quadrupedal locomotion characterized by a doubling of forelimb stepping in relation to unaffected hindlimb stepping (2FL-1HL) after blockade of 5-HT7 receptors but not after blockade of 5-HT2A receptors. The 2FL-1HL pattern, although transient, was observed as a stable form of fore-hindlimb coupling during quadrupedal locomotion. We suggest that modulation of the 5-HT7 receptors on interneurons located in lamina VII with ascending projections to the forelimb spinal network can be responsible for the 2FL-1HL locomotor pattern. In support, our immunohistochemical analysis of the lumbar spinal cord demonstrated the presence of the 5-HT7 immunoreactive cells in the lamina VII, which were rarely 5-HT2A immunoreactive.
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Locomoção/genética , Receptor 5-HT2A de Serotonina/genética , Receptores de Serotonina/genética , Traumatismos da Medula Espinal/genética , Animais , Ciproeptadina/farmacologia , Estimulação Elétrica , Eletromiografia , Membro Anterior/efeitos dos fármacos , Membro Anterior/fisiopatologia , Membro Posterior/efeitos dos fármacos , Membro Posterior/fisiopatologia , Humanos , Locomoção/efeitos dos fármacos , Região Lombossacral/fisiopatologia , Ratos , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Serotonina/genética , Serotonina/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Coluna Vertebral/efeitos dos fármacos , Coluna Vertebral/fisiopatologiaRESUMO
Background and Objectives: obesity and blood pressure disorders are one of the main risk factors for antenatal, intra, postpartum, and neonatal complications. In preeclampsia (PE), the placental hypoxia leads to vascular endothelium dysfunction, cell necrosis, and apoptosis. This condition is associated with the release of free fetal DNA (cffDNA) circulating in plasma. The disturbance of the efficiency of vasodilatation and blood pressure regulation in PE can be confirmed by analyzing the apelin, salusin, and prosalusin. This study aimed to assess the influence of obesity on cffDNA, and the effectiveness of maintaining normal blood pressure in patients with preeclampsia and gestational hypertension. Material and Methods: the research material was blood serum and oral mucosa swabs, obtained from 168 patients. Pregnant women were divided into the following: a control group (C)-67 women; a gestational hypertension group (GH)-35 patients; a preeclampsia with obesity group (PE + O) (pre-gravid BMI > 30)-23 patients. The rest were lean preeclamptic women (PE)-66 patients-(pre-gravid BMI < 25 in 43 women). Results: the cffDNA was observed in 1.50% of women in the C group, in 2.45% in the GH group, but in 18.18% of lean patients with preeclampsia. The cffDNA was detected in 58% of obese pregnant women with PE. The greater the placental hypoxia was in preeclampsia, the less efficient the hypotensive mechanisms, according to an analysis of the studied adipokines. The prosalusin concentration was significantly lower in the PE group with cffDNA than in the PE group without it (p = 0.008). Apelin was higher in the PE group with cffDNA (p = 0.006) compared to other groups. The same results were also observed in the subgroup with obesity. Conclusion: in preeclamptic women, obesity seems to act as an additive factor of placental damage by means of the dysregulation of hypotensive mechanisms.
Assuntos
Hipertensão Induzida pela Gravidez , Obesidade Materna , Pré-Eclâmpsia , Pressão Sanguínea , Feminino , Humanos , Obesidade/complicações , Placenta , GravidezRESUMO
OBJECTIVE: It is well known that mitochondrial dysfunctions are involved in tumorigenesis. A special interest of scientists is mitochondrial ND1 gene (mtND1). Recently detected mutations in the mtND1 can disrupt the normal activity of complex I and affect oxidative phosphorylation, thus leading to increase reactive oxygen species production. This study was undertaken to determine the alternations in the mtND1 and evaluate their association with development of precancerous lesions and cervical cancer. METHODS: In the study 29 cervical cancer, 28 low grade squamous intraepithelial lesion (L-SIL) and 30 high grade squamous intraepithelial lesion (H-SIL) HPV positive fragments tissue were screened for the presence of mtND1 mutations. RESULTS: Our study showed that mutations in the mtND1 gene were detected in patients with precancerous stage, as well as cervical cancer. We have identified 12 point mutations in 116 analyzed precancerous and cancer samples HPV positive. Most detected missense mutations were previously described, except one (p. M156K) with Grantham value 95. The lower expression of mRNA ND1 was detected in cervical cancer cases and in all samples in which mtND1 mutations were identified. Our analyses revealed that level of ROS production was higher in cervical cancer tissues and all cases characterized by mtND1 mutations. CONCLUSIONS: We hypothesize that mutations in MT-ND1 observed in H-SIL and cancer could activate cervical carcinogenesis by increased ROS production.
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NADH Desidrogenase/genética , Lesões Intraepiteliais Escamosas/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Carcinogênese/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genoma Mitocondrial/genética , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Lesões Intraepiteliais Escamosas/patologia , Lesões Intraepiteliais Escamosas/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
INTRODUCTION: Neural tube defects (NTDs) are a group of heterogeneous congenital anomalies of the central nervous system (CNS). Acrania is a non-NTD congenital disorder related to the CNS. It can transform into anencephaly through the acrania-exencephaly-anencephaly sequence (AEAS). In AEAS, the cerebral tissue is not protected and is gradually destroyed due to exposure to the harmful effect of amniotic fluid and mechanical injuries. These lead to exencephaly and then into anencephaly. In contrast to primary anencephaly (NTDs), this type of anencephaly authors suggests calling secondary anencephaly. OBJECTIVE: Analysis of the known prenatal ultrasonography (US) signs associated with AEAS. Simultaneously, the authors propose a new sign in the differentiation of acrania from exencephaly and anencephaly, called the "beret" sign. METHODS: It is a two-centre retrospective observational study. As part of the study, 4060 US scans were analyzed. RESULTS: In 10 cases, the absence of calvarium was diagnosed, allowing recognition of either AEAS stages or primary anencephaly. In 5 cases, cerebral structures were enclosed by an inertial rippled thin membrane, with a smooth outer contour. Between the described membrane and the brain structures, a thin anechoic space corresponding to cerebrospinal fluid was observed. This sign was defined as the "beret" sign. In these cases, acrania was diagnosed. In three cases calvarium was missing. The brain structures had an irregular appearance, did not wave and remained motionless. The outer contour was unequal as if divided into lobes. Amniotic fluid was anechoic. Exencephaly was diagnosed in these cases. In two cases calvarium, brain structures, and meninges were missing. The "frog eyes" sign and slightly echogenic amniotic fluid were visible. In this case, anencephaly was diagnosed. CONCLUSIONS: The "beret" sign seems to be a promising tool in the diagnosis of acrania. Furthermore, echogenicity of amniotic fluid could be useful during differentiation between primary and secondary anencephaly.
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Anencefalia/diagnóstico por imagem , Defeitos do Tubo Neural/diagnóstico por imagem , Crânio , Ultrassonografia Pré-Natal/métodos , Líquido Amniótico , Anencefalia/complicações , Anencefalia/diagnóstico , Biomarcadores , Encéfalo/anormalidades , Feminino , Humanos , Recém-Nascido , Defeitos do Tubo Neural/complicações , Gravidez , Estudos Retrospectivos , Crânio/anormalidades , Crânio/diagnóstico por imagem , UltrassonografiaRESUMO
Activity modulation of drug metabolism enzymes can change the biotransformation of chemotherapeutics and cellular responses induced by them. As a result, drug-drug interactions can be modified. Acridinone derivatives, represented here by C-1305 and C-1311, are potent anticancer drugs. Previous studies in non-cellular systems showed that they are mechanism-based inhibitors of cytochrome P4503A4 and undergo glucuronidation via UDP-glucuronosyltranspherase 1A10 isoenzyme (UGT1A10). Therefore, we investigated the potency of these compounds to modulate P4503A4 and UGT1A10 activity in breast MCF-7 and colon HCT116 cancer cells and their influence on cytotoxicity and cellular response in cells with different expression levels of studied isoenzymes. We show that C-1305 and C-1311 are inducers of not only P4503A4 but also UGT1A10 activity. MCF-7 and HCT116 cells with high P4503A4 activity are more sensitive to acridinone derivatives and undergo apoptosis/necrosis to a greater extent. UGT1A10 was demonstrated to be responsible for C-1305 and C-1311 glucuronidation in cancer cells and glucuronide products were excreted outside the cell very fast. Finally, we show that glucuronidation of C-1305 antitumor agent enhances its pro-apoptotic properties in HCT116 cells, while the cytotoxicity and cellular response induced by C-1311 did not change after drug glucuronidation in both cell lines.
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Acridinas/farmacologia , Aminoacridinas/farmacologia , Antineoplásicos/farmacologia , Citocromo P-450 CYP3A/metabolismo , Glucuronosiltransferase/metabolismo , Triazóis/farmacologia , Apoptose , Biotransformação , Linhagem Celular Tumoral , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glucuronídeos/metabolismo , Células HCT116 , Humanos , Isoenzimas , Células MCF-7 , Potencial da Membrana Mitocondrial , Necrose , Especificidade por SubstratoRESUMO
Intraspinal grafting of serotonergic (5-HT) neurons was shown to restore plantar stepping in paraplegic rats. Here we asked whether neurons of other phenotypes contribute to the recovery. The experiments were performed on adult rats after spinal cord total transection. Grafts were injected into the sub-lesional spinal cord. Two months later, locomotor performance was tested with electromyographic recordings from hindlimb muscles. The role of noradrenergic (NA) innervation was investigated during locomotor performance of spinal grafted and non-grafted rats using intraperitoneal application of α2 adrenergic receptor agonist (clonidine) or antagonist (yohimbine). Morphological analysis of the host spinal cords demonstrated the presence of tyrosine hydroxylase positive (NA) neurons in addition to 5-HT neurons. 5-HT fibers innervated caudal spinal cord areas in the dorsal and ventral horns, central canal, and intermediolateral zone, while the NA fiber distribution was limited to the central canal and intermediolateral zone. 5-HT and NA neurons were surrounded by each other's axons. Locomotor abilities of the spinal grafted rats, but not in control spinal rats, were facilitated by yohimbine and suppressed by clonidine. Thus, noradrenergic innervation, in addition to 5-HT innervation, plays a potent role in hindlimb movement enhanced by intraspinal grafting of brainstem embryonic tissue in paraplegic rats.
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Tronco Encefálico/transplante , Transplante de Tecido Encefálico/métodos , Regeneração Nervosa/fisiologia , Paraplegia/cirurgia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/cirurgia , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Tronco Encefálico/embriologia , Clonidina/farmacologia , Feminino , Membro Posterior/efeitos dos fármacos , Membro Posterior/inervação , Membro Posterior/fisiopatologia , Locomoção/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Paraplegia/fisiopatologia , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia , Ioimbina/farmacologiaRESUMO
INTRODUCTION: The treatment outcomes of patients with advanced/metastatic melanoma were poor before the use of new therapeutic options. MATERIAL AND METHODS: A retrospective analysis was conducted among 287 patients with unresectable stage III and stage IV melanoma treated at the Maria Sklodowska-Curie National Research Institute of Oncology Cracow Branch, from 2013 to 2019. All enrolled patients were treated with immunotherapy (IT; consisting of pembrolizumab/nivolumab, or ipilimumab) or target therapy (TT; consisting of vemurafenib ±cobimetinib or dabrafenib ±trametinib) in at least one treatment line. RESULTS: mutation was detected in 152 (55%) patients. In general, the majority of patients (92%) were in very good or good condition (Eastern Cooperative Oncology Group [ECOG] 0 or 1). Brain metastasis was detected in 64 (22%) patients. Median OS and PFS in the experimental group from the beginning of the first-line treatment were 14.9 and 6.7 months, respectively. Across the study population, as a first-line treatment patients received IT, TT as well as CHT, and the median OS was 19.2, 12.6 and 15.9 months, respectively. Multivariate analysis confirmed that normal LDH levels, no brain metastases, ECOG 0, and objective response to the treatment were strong predictors of longer OS. For PFS, absence of brain metastases, ECOG 0, and treatment response were found to be predictive factors on multivariate analysis. CONCLUSIONS: The administration of new therapies for the treatment of patients with advanced/disseminated melanoma significantly prolonged survival in this group of patients. Nevertheless, further studies should be conducted to assess the effectiveness of various sequences of treatment.
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BACKGROUND: The potential HPV transmission route includes horizontal transmission "in utero" and vertical transmission from parents. Less is known about the role of child's father as a potential source of HPV infection and involved in the pathogen's epidemic chain. A possible consequence of perinatal infection includes HPV-related childhood diseases and carrying the risk of cervical cancer development in female offspring. In view of the evidence, studies of HPV co-occurrence in one or both parents and their offspring seem vital for the implementation of respective preventive measures. Consequently, the aim of this study was to determine the incidence of common HPV 16/18 infections in newborns and their parents, and to assess its role of the periconceptional transmission. METHODS: To determine the incidence of common HPV infections in newborns from single pregnancies and their parents. The study included 146 pregnant women, as well as their partners, and newborns. They were tested for the presence of HPV 16/18 DNA using the PCR method. HPV types 16 and/or 18 were identified using type-specific PCR primers. The quality of the extracted DNA was evaluated by PCR using PC03/PC04 ß-globin-specific primers. The relationship between the presence of neonatal and parental HPV infection was analyzed using a multivariable regression model. Calculations were carried out with the Statistica 10. RESULTS: The presence of HPV DNA was detected in 19 (13,01%) newborns, 28 (19,18%) mothers, and 20 (13,7%) fathers. The viral DNA was detected in 14 newborns delivered by HPV-positive mothers (OR = 26,08; CI: 8,07-84,31, p < 0.001), 12 descendants of HPV-positive fathers (OR = 22,13; CI: 6,97-70,27, p < 0.001), and 10 children originating from two infected parents (OR = 24,20; CI: 6,84-85,57 p < 0.001). Those findings points to a increase risk of an acquired infection in newborns with HPV-positive parents. CONCLUSION: Our findings suggest the possible role of the periconceptional transmission in the mode of acquired HPV 16/18 infections.
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Infecções por Papillomavirus/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Adolescente , Adulto , DNA Viral/sangue , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Incidência , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Mães , Infecções por Papillomavirus/virologia , Pais , Polônia/epidemiologia , Reação em Cadeia da Polimerase , Gravidez , Adulto JovemRESUMO
The umbilical cord is the only connection between the mother and the fetus, through which it is possible to transport respiratory gases, nutrients, and metabolites. Thanks to the umbilical cord, the fetus has also the ability to move, which is necessary for its proper psychomotor development. The correct structure and function of umbilical vessels and the entire umbilical cord determine the possibility of proper development and survival of the fetus. Umbilical cord anatomy should be assessed in the ultrasound examination in the first trimester. It is of vital importance to confirm the correct number of umbilical vessels and their intra-abdominal course, as well as carefully assessing the abdominal and placental insertion sites. In the latter half of pregnancy, the use of the Doppler imaging enables assessment of the function of the fetal-placental vessels, thus providing valuable information about the condition of the fetus.
Assuntos
Diagnóstico Pré-Natal/métodos , Ultrassonografia Pré-Natal/métodos , Cordão Umbilical/anormalidades , Cordão Umbilical/diagnóstico por imagem , Feminino , Sofrimento Fetal/diagnóstico por imagem , Feto/diagnóstico por imagem , Feto/metabolismo , Humanos , GravidezRESUMO
BACKGROUND: Persistent right umbilical vein (PRUV) is usually an isolated finding but it may be accompanied by other fetal malformations. AIMS: We aimed to determine the incidence of prenatally diagnosed PRUV in a referral population, assess the neonatal outcome and discuss the findings together with those from previous publications. MATERIALS AND METHODS: A total of 2360 women with low-risk singleton pregnancies were examined in the second and third trimesters. A transabdominal convex volume transducer was used. B-mode was applied in each patient. Scanning of the venous system included imaging of the target vessels with two-dimensional colour Doppler mapping. The diagnosis of PRUV was made in a transverse section of the fetal abdomen. Three-dimensional ultrasounds were performed as necessary, when anomalous cases were encountered. RESULTS: The incidence of PRUV in our population was 12/2360 = 0.5%, and it was higher than in other retrospective studies. In 75% (n = 9), PRUV was an isolated finding where delivery was uneventful and the postnatal outcome was favourable. In two cases PRUV was accompanied by omphalocele, and in one case by tetralogy of Fallot and single umbilical artery. CONCLUSIONS: PRUV is an uncommon prenatal finding. Screening for this anomaly can be easily performed in all pregnant patients. A diagnosis of PRUV should be followed by a thorough fetal morphology scan in order to exclude any other malformations, especially those of the cardiovascular system.
Assuntos
Anormalidades Congênitas/epidemiologia , Ultrassonografia Pré-Natal , Veias Umbilicais/anormalidades , Adolescente , Adulto , Anormalidades Congênitas/diagnóstico por imagem , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Polônia/epidemiologia , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Veias Umbilicais/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND Mesenchymal stromal cells, MSCs, show expression of specific antigens on their surface. The aim of the study is to assess the phenotype of stem cells like isolated from the umbilical cord with respect to the presence of surface antigens CD34, CD90, and CD105 and differences in the expression of surface antigens in cells isolated from freshly sampled material in comparison with the phenotype of cells from in vitro culture. MATERIAL AND METHODS Stem cells collected from the umbilical cord from healthy patients and then cultured in vitro. To assess the phenotype of stem cells, cytometric analysis was carried out. To assess the phenotype of cells we used fluorescently labelled monoclonal antibodies: APC Mouse anti-human CD34, PC5 Mouse anti-human CD90 and PE Mouse anti-human CD105. RESULTS In the case of cells from the umbilical cord and then cultured in vitro for the period of 10-14 days CD34 expression is lower (69,5%) in comparison with the group of cells not cultured. Not cultured cells were demonstrated 37% of cells co-expression of antigens CD34 and CD105, over 21% of CD34/CD90 cells and over 24% of CD105/CD90. Cultured cells group was showed higher percentage of CD90, CD105, CD34/CD105, CD34/CD90, CD105/CD90 in comparison with not cultured cells. CONCLUSIONS Our reults suggested that adherent cells population from umbilical cord, demonstrate CD34 expression In vivo. Moreover, the phenotype of MSCs, mainly in the context of CD34 expression, may vary depending on the place of collection of cells and the length of growing the cell culture.
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Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Cordão Umbilical/citologia , Antígenos CD/metabolismo , Adesão Celular/genética , Adesão Celular/fisiologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Proliferação de Células , Separação Celular , Células Cultivadas , Sangue Fetal/citologia , Citometria de Fluxo , Humanos , Células-Tronco Mesenquimais/metabolismo , Fenótipo , Células-TroncoRESUMO
OBJECTIVES: The etiology of gestational diabetes mellitus (GDM) remains to be fully elucidated. Elevated risk for type 2 diabetes in patients with history of GDM and for GDM in women with familial history of diabetes may suggest that GDM and type 2 diabetes share a common genetic and environmental background. The TCF7L2 (Transcription Factor 7 Like 2) gene is one of the most important genetic factors of the established correlation with type 2 diabetes, and it may also play a role in the pathophysiology of GDM. The aim of the study was to assess the influence of two polymorphisms of the TCF7L2 gene (rs7901695 and rs7903146), which are associated with the development of type 2 diabetes, in women with GDM. MATERIAL AND METHODS: The study included 50 women with glucose tolerance disorders diagnosed for the first time during the current pregnancy. Single nucleotide polymorphisms (SNPs) were genotyped using allelic discrimination. The results were confirmed using the sequencing method. Selected clinical parameters were also analyzed. RESULTS: No correlation between the studied polymorphisms of the TCF7L2 gene and GDM was observed. Glycemic control with diet or diet and insulin was associated with better control of the weight gain during pregnancy. CONCLUSIONS: No correlation between rs7903146 and rs7901695 polymorphisms of the TCF7L2 gene and GDM was found. Glycemic control with diet or diet and insulin is associated with better control of the weight gain during pregnancy.