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1.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064719

RESUMO

Inflammation is a major cause of several chronic diseases and is reported to be recovered by the immuno-modulation of mesenchymal stem cells (MSCs). While most studies have focussed on the anti-inflammatory roles of MSCs in stem cell therapy, the impaired features of MSCs, such as the loss of homeostasis by systemic aging or pathologic conditions, remain incompletely understood. In this study, we investigated whether the altered phenotypes of human placenta-derived MSCs (hPD-MSCs) exposed to inflammatory cytokines, including TNF-α and IFN-γ, could be protected by MIT-001, a small anti-inflammatory and anti-necrotic molecule. MIT-001 promoted the spindle-like shape and cytoskeletal organization extending across the long cell axis, whereas hPD-MSCs exposed to TNF-α/IFN-γ exhibited increased morphological heterogeneity with an abnormal cell shape and cytoskeletal disorganization. Importantly, MIT-001 improved mitochondrial distribution across the cytoplasm. MIT-001 significantly reduced basal respiration, ATP production, and cellular ROS levels and augmented the spare respiratory capacity compared to TNF-α/IFN-γ-exposed hPD-MSCs, indicating enhanced mitochondrial quiescence and homeostasis. In conclusion, while TNF-α/IFN-γ-exposed MSCs lost homeostasis and mitochondrial quiescence by becoming over-activated in response to inflammatory cytokines, MIT-001 was able to rescue mitochondrial features and cellular phenotypes. Therefore, MIT-001 has therapeutic potential for clinical applications to treat mitochondrion-related inflammatory diseases.


Assuntos
Citoesqueleto/fisiologia , Células-Tronco Mesenquimais/fisiologia , Mitocôndrias/fisiologia , Compostos Orgânicos/farmacologia , Placenta/citologia , Citoesqueleto/efeitos dos fármacos , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Consumo de Oxigênio , Placenta/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Espécies Reativas de Oxigênio/metabolismo
2.
BMC Genomics ; 22(1): 410, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082698

RESUMO

BACKGROUND: There are two genetically distinct subspecies of cattle, Bos taurus taurus and Bos taurus indicus, which arose from independent domestication events. The two types of cattle show substantial phenotypic differences, some of which emerge during fetal development and are reflected in birth outcomes, including birth weight. We explored gene expression profiles in the placenta and four fetal tissues at mid-gestation from one taurine (Bos taurus taurus; Angus) and one indicine (Bos taurus indicus; Brahman) breed and their reciprocal crosses. RESULTS: In total 120 samples were analysed from a pure taurine breed, an indicine breed and their reciprocal cross fetuses, which identified 6456 differentially expressed genes (DEGs) between the two pure breeds in at least one fetal tissue of which 110 genes were differentially expressed in all five tissues examined. DEGs shared across tissues were enriched for pathways related to immune and stress response functions. Only the liver had a substantial number of DEGs when reciprocal crossed were compared among which 310 DEGs were found to be in common with DEGs identified between purebred livers; these DEGs were significantly enriched for metabolic process GO terms. Analysis of DEGs across purebred and crossbred tissues suggested an additive expression pattern for most genes, where both paternal and maternal alleles contributed to variation in gene expression levels. However, expression of 5% of DEGs in each tissue was consistent with parent of origin effects, with both paternal and maternal dominance effects identified. CONCLUSIONS: These data identify candidate genes potentially driving the tissue-specific differences between these taurine and indicine breeds and provide a biological insight into parental genome effects underlying phenotypic differences in bovine fetal development.


Assuntos
Bovinos/genética , Domesticação , Impressão Genômica , Alelos , Animais , Cruzamento , Cruzamentos Genéticos , Feminino , Expressão Gênica , Gravidez
3.
Sci Total Environ ; 783: 146984, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34088118

RESUMO

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), a class of persistent endocrine-disrupting chemicals, are widely used in consumer products due to their unique amphiphilic properties. Previous epidemiological studies suggest association of maternal PFASs exposure and adverse pregnancy outcomes, while evidences about the association are inconsistent. The aim of this systematic review and meta-analysis is to assess the relationship of maternal PFASs exposure and adverse pregnancy outcomes. Twenty-one relevant studies were identified from three databases before 2020. The quality, heterogeneity and possibility of publication bias of included studies were evaluated by Newcastle-Ottawa Scale, Q-statistic and Begg's test, respectively. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were obtained by means of random-effects meta-analysis models. Meta-analysis results revealed that maternal exposure to perfluorooctane sulfonic acid (PFOS) may have a positive association with preterm birth (OR = 1.20, 95% CI: 1.04, 1.38). The pooled estimates also showed limited evidence of association between maternal perfluorononanoic acid (PFNA) exposure and miscarriage (OR = 1.48, 95% CI: 0.92, 2.38) with obvious heterogeneity (I2 = 93.9, p < 0.01). However, no such significant associations were found between the other PFASs and miscarriage, stillbirth and preterm birth. In addition, the subgroup analyses showed that studies on the relationship of maternal PFASs exposure and miscarriage were mainly contributed by developed countries. The meta-analysis results indicated maternal exposure to PFOS can increase the risk of preterm birth. The results of the included studies are inconsistent and the effects of PFASs on human health are complex. Further studies with enough samples are required to verify these findings.


Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Fluorcarbonetos , Nascimento Prematuro , Feminino , Fluorcarbonetos/toxicidade , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia
4.
J Pak Med Assoc ; 71(5): 1332-1336, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34091609

RESUMO

Objectives: To find the association between interleukin-1 receptor-associated kinase 1 rs3027898 gene polymorphism and preeclampsia. METHODS: The case-control study was conducted from October, 2018 to September, 2019 at the Railway General Hospital and the Department of Biochemistry, Islamic International Medical College, Rawalpindi, Pakistan, and comprised patients diagnosed with preeclampsia and healthy controls. The interleukin receptor-associated kinase-1 polymorphism was determined using multiplex tetra primer amplification refractory mutation system polymerase chain reaction. Outcomes were determined in terms of association of interleukin receptor-associated kinase-1 with preeclampsia. Data was analysed using SPSS 22. RESULTS: Of the 160 subjects, 80(50% were cases with a mean age of 30±5.3 years and 80(50%) were controls with a mean age of 27±3.7 years. AC genotype was seen in 45(56.25%) cases and 30(37.5%) controls, AA genotype in 25(31.25%) cases and 30(37.5%) controls, while CC genotype was seen in 10(12.5%) cases and 20(25%) controls (p>0.05). CONCLUSIONS: There was no significant association of interleukin receptor-associated kinase-1 genotypes with preeclampsia.


Assuntos
Pré-Eclâmpsia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Quinases Associadas a Receptores de Interleucina-1 , Paquistão/epidemiologia , Polimorfismo Genético , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/genética , Gravidez , Receptores de Interleucina-1 , Adulto Jovem
5.
Mol Biol (Mosk) ; 55(3): 441-459, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34097679

RESUMO

Preeclampsia (PE) is a severe hypertensive pathology and affects 2-8% of pregnancies worldwide. Its etiopathogenesis is poorly understood, and prognostic biomarkers and effective treatments are unavailable for this pregnancy complication, determining the high rates of maternal and perinatal morbidity and mortality. Racial and ethnic differences in PE incidence are of interest to study in terms of evolutionary medicine because such variability can be considered as a side effect of adaptive changes that have occurred in the genetic structure of modern populations since the dispersal of Homo sapiens from Africa. Genetic diversity at 10 regulatory single nucleotide polymorphisms (rSNPs) associated with PE was studied in North Eurasian populations and world populations of the 1000 Genomes Project. The role of natural selection in the formation of this genetic diversity was assessed at the microevolutionary level. High interpopulation diversity was observed with the greatest contribution being made by allele frequencies of NDRG1 rs3802252 (FST = 0.157). Signatures of natural selection were detected for rs10423795 of LHB, rs2167270 of LEP, rs2227262 and rs3802252 of NDRG1, rs56153523 and rs8109071 of SYDE1, and rs72959687 of INHA. The results are consistent with two evolutionary hypotheses of PE, namely, those of ancestral susceptibility and genetic conflicts.


Assuntos
Pré-Eclâmpsia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , Gravidez , Seleção Genética
6.
BMJ Case Rep ; 14(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099450

RESUMO

We describe a cluster of six SARS-CoV-2 infections occurring in a crowded neonatal unit in Botswana, including presumed transmission among mothers, postnatal mother-to-neonate transmission and three neonate-to-healthcare worker transmissions. The affected neonate, born at 25 weeks' gestation weighing 785 g, had a positive SARS-CoV-2 test at 3 weeks of age which coincided with new onset of hypoxaemia and worsening respiratory distress. Because no isolation facility could accommodate both patient and mother, they were separated for 10 days, during which time the patient was switched from breastmilk to formula. Her subsequent clinical course was marked by several weeks of supplemental oxygen, sepsis-like presentations requiring additional antibiotics and bronchopulmonary dysplasia. Despite these complications, adequate growth was achieved likely due to early initiation of nutrition. This nosocomial cluster highlights the vulnerabilities of neonates, caregivers and healthcare workers in an overcrowded environment, and underscores the importance of uninterrupted bonding and breast feeding, even during a pandemic.


Assuntos
COVID-19 , Infecção Hospitalar , Complicações Infecciosas na Gravidez , Botsuana/epidemiologia , Infecção Hospitalar/epidemiologia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Gravidez , SARS-CoV-2
7.
BMJ Case Rep ; 14(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099451

RESUMO

A late preterm infant was born to a diabetic mother on a background of reduced fetal movements and a poor CTG. It was noted immediately at birth that there was pathology in both upper limbs. Targeted investigation led to the diagnosis of bilateral upper limb arterial thromboses. Prompt assessment and multidisciplinary discussion led to an individualised management plan resulting in a positive outcome.


Assuntos
Nascimento Prematuro , Trombose , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Parto , Gravidez
8.
BMJ Case Rep ; 14(6)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083183

RESUMO

Extra-axial haemorrhage following epidural anaesthesia is extremely rare. We present the case of an 18-year-old G1P0 woman with Alport syndrome who had a ventouse delivery for failure to progress that was complicated by a postpartum tonic-clonic seizure. Clinically, and confirmed radiologically, the patient was found to have experienced an extra-axial haemorrhage (extradural and subdural haemorrhage) secondary to a cerebrospinal fluid leak caused by a dural puncture during epidural anaesthesia. Differentiating between postdural puncture headache, subdural haemorrhage and extradural haemorrhage can be extremely challenging, but it is important to consider these rare conditions when evaluating patients presenting with postpartum headache and seizure.


Assuntos
Anestesia Epidural , Nefrite Hereditária , Cefaleia Pós-Punção Dural , Adolescente , Anestesia Epidural/efeitos adversos , Placa de Sangue Epidural , Vazamento de Líquido Cefalorraquidiano , Feminino , Hematoma Subdural , Humanos , Gravidez
9.
Wei Sheng Yan Jiu ; 50(3): 460-465, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34074369

RESUMO

OBJECTIVE: To explore the relationship between dietary inflammatory index(DII), serum interleukin-6(IL-6) of late pregnant women and infant birth weight. METHODS: This study was conducted in late pregnant women who received antenatal care at the Maternal and Children& apos; s Hospital of Baiyun and Yuexiu District in Guangzhou, China between September 2010 and February 2011. Tree consecutive 24-h diet recalls, pre-pregnancy body mass index, maternal education level and etc were collected. DII score was calculated based on data of dietary surveys. Participant were dived into anti-inflammatory group(T1), neutral group(T2) and pro-inflammatory group(T3) according to the tertiles of DII score. Maternal and infant anthropometric profile(n=456) and level of maternal serum IL-6(n=308) were measured. Structrural equation modeling(SEM) was used to explore the relationship between DII, IL-6 and birth weight. RESULTS: In 456 women, the mean DII score was 0. 02±1. 08. Women performed anti-inflammatory diet had higher intake of grain and potato, vegetables, energy, fiber, minerals, vitamins and unsaturated fatty acids, but lower intakes of fruits, diary, fat(% energy) and protein from animal food(P& lt; 0. 05). Average infant birth weight and level of maternal serum IL-6 were(3238. 1±376. 4)g and 4. 05(2. 02, 10. 14) pg/mL respectively. DII of pregnant women was positively correlated with maternal serum IL-6(r=0. 144, P& lt; 0. 05), and IL-6 was negatively correlated with birth weight(r=-0. 184, P& lt; 0. 05). SEM indicated that maternal serum IL-6 may be a mediator in the association between DII and birth weight. CONCLUSION: The diet of pregnant women may change the serum level of IL6, and then affect infant birth weight.


Assuntos
Peso ao Nascer , Dieta , Interleucina-6 , Gestantes , China , Feminino , Humanos , Recém-Nascido , Inflamação , Interleucina-6/sangue , Gravidez
10.
Chemosphere ; 276: 130213, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34088095

RESUMO

Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by a variety of alternatives in consumer products. Due to their structural similarity to BPA, these alternatives are under surveillance, however, for potential endocrine disruption. Understanding the materno-fetal transfer of these BPA-related alternatives across the placenta is therefore crucial to assess prenatal exposure risks. The objective of the study was to assess and compare the placental transfer of a set of 15 selected bisphenols (BPs) (BP 4-4, BPA, BPAF, BPAP, 3-3 BPA, BPB, BPBP, BPC, BPE, BPF, BPFL, BPM, BPP, BPS and BPZ) using the ex vivo human placental perfusion model. The UHPLC-MS/MS method for simultaneous quantification of these BPs in perfusion media, within a concentration range of 0.003-5 µM, was able to measure placenta transfer rates as low as 0.6%-4%. Despite their structural similarities, these BPs differed greatly in placental transport efficiency. The placental transfer rates of BP4-4, BPAP, BPE, BPF, 3-3BPA, BPB, BPA were similar to that of antipyrine, indicating that their main transport mechanism was passive diffusion. By contrast, the placental transfer rates of BPFL and BPS were very limited, and intermediate for BPBP, BPZ, BPC, BPM, BPP and BPAF, suggesting weak diffusional permeability and/or that their passage might involve efflux transport. These placental transfer data will be particularly useful for predicting the fetal exposure of this important class of emerging contaminants.


Assuntos
Placenta , Espectrometria de Massas em Tandem , Compostos Benzidrílicos , Feminino , Humanos , Perfusão , Fenóis , Gravidez
11.
Wiad Lek ; 74(5): 1065-1068, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34090265

RESUMO

OBJECTIVE: The aim: To study the clinical efficciency of the proposed scheme of gingivitis treatment in women with physiological course of pregnancy. PATIENTS AND METHODS: Materials and methods: Clinical approbation of the proposed complex of therapeutic and prophylactic measures was carried out in 32 pregnant women with gingivitis, aged 18 to 35 years. The efficiency of the treatment was assessed by the dynamics of the clinical picture, the index assessment of an oral hygiene and the periodontium condition in each trimester of pregnancy. RESULTS: Results: According to the data of performed observations, the high efficiency of the proposed treatment scheme is shown: 84.4% in the main group versus 46.9% in the control group. It has been clinically proven that the proposed scheme of inflammatory periodontal diseases treatment in terms of therapeutic efficiency exceeds the generally accepted basic treatment. CONCLUSION: Conclusions:The use of the proposed complex of therapeutic and prophylactic measures in the main group of patients contributed to the elimination of the inflammatory process in the periodontal tissues, suspended the progression of existing diseases, made it possible to prevent the emergence of new nosological forms, improved the condition of the oral hygiene, which makes it possible to recommend it for treatment of periodontal diseases in pregnant women.


Assuntos
Gengivite , Doenças Periodontais , Complicações na Gravidez , Feminino , Gengivite/prevenção & controle , Humanos , Doenças Periodontais/prevenção & controle , Periodonto , Gravidez , Complicações na Gravidez/prevenção & controle , Gestantes
12.
Orv Hetil ; 162(23): 924-926, 2021 06 06.
Artigo em Húngaro | MEDLINE | ID: mdl-34091439

RESUMO

Összefoglaló. A veseátültetés a legnagyobb reményt nyújtja a végstádiumú vesebetegségben szenvedo nok számára, akik teherbe kívánnak esni. A veseátültetett beteg terhessége továbbra is kihívást jelent az immunszuppresszív gyógyszerek mellékhatásai, az allograftfunkció romlásának kockázata, a praeeclampsia és a magas vérnyomás káros anyai szövodményeinek rizikója, valamint a koraszülés, az alacsony születési súly kockázata miatt. A terhesség alatt nagy a magas vérnyomás kialakulásának kockázata, a szérum-kretaininszint emelkedik, és a terhesség végére proteinuria is kialakulhat. Az ajánlott fenntartó immunszuppresszió terhes noknél a kalcineurininhibitorok (takrolimusz/ciklosporin) és alacsony dózisú szteroid adása, melyek biztonságosnak tekinthetok. Fontos, hogy a gyermekvállalási tanácsadás már a vesetranszplantáció elott megkezdodjön, és a transzplantációt követoen minden klinikai kontroll megtörténjen. Orv Hetil. 2021; 162(23): 924-926. Summary. Kidney transplantation offers the best hope to women with end-stage renal disease who wish to become pregnant. Pregnancy in a kidney transplant recipient continues to remain challenging due to side effects of immunosuppressive medication, risk of deterioration of allograft function, risk of adverse maternal complications of preeclampsia and hypertension, and risk of adverse fetal outcomes of premature birth, low birth weight, and small for gestational age infants. The factors associated with poor pregnancy outcomes include the presence of hypertension, serum creatinine greater than normal range and proteinuria. The recommended maintenance immunosuppression in pregnant women is calcineurin inhibitors (tacrolimus/cyclosporine) and low-dose steroid which are considered safe. It is important that counseling for childbearing should start as early as prior to getting a kidney transplant and should be done at every clinic visit after transplant. Orv Hetil. 2021; 162(23): 924-926.


Assuntos
Hipertensão , Transplante de Rim , Ciclosporina , Feminino , Humanos , Doadores Vivos , Gravidez , Resultado da Gravidez
13.
J Pak Med Assoc ; 71(5): 1319-1325, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34091607

RESUMO

OBJECTIVE: To determine the effects of an exercise programme for core muscle strengthening in patients with low back pain after caesarean section. Methods: The single-blind randomised controlled trail was conducted from August 2018 to January 2019 at the Helping Hand for Relief and Development Comprehensive Rehabilitation Centre, Chakwal, Pakistan, and comprised post-caesarean section women aged 25-40 years with low back pain. Patients were randomised into supervised group I and unsupervised group II using the sealed envelope method. Group I received supervised core stability exercise programme, while group II received unsupervised, home-based core stability exercise programme. Baseline and post-intervention values were compared for numeric pain rating scale, Oswestry disability index, inclinometer and core stability assessment. Data was analysed using SPSS 21. RESULTS: Of the 30 subjects, there were 15(50%) in each of the two groups. There was no significant difference at baseline between the groups (p>0.05). Post-intervention results showed significant intra-group and inter-group differences (p<0.05) with respect to all parameters. No improvement was observed for right and left side bending (p>0.05). CONCLUSIONS: Supervised core stability exercise programme was more effective in reducing pain and disability, and improved core muscle activation than unsupervised, home-based core exercise programme.


Assuntos
Dor Lombar , Cesárea , Terapia por Exercício , Feminino , Humanos , Dor Lombar/terapia , Músculos , Paquistão , Gravidez , Método Simples-Cego
14.
J Pak Med Assoc ; 71(5): 1446-1449, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34091632

RESUMO

OBJECTIVE: To perform a clinical audit of the practices related to the management of third and fourth degree perineal tears. METHODS: The retrorspective study was conducted in 2019 at the Aga Khan University Hospital, Karachi, and comprised medical records from January 2008 to December 2018 of women having singleton term vaginal delivery and sustaining obstetric anal sphincter injuries. The change in practices regarding tear management was compared with a previous audit done at the same institution in 2008. Data was analysed using SPSS 20. RESULTS: Of the 25,370 deliveries, 142(0.56%) sustained obstetric anal sphincter injuries. There was a significant increase compared to the previous audit in terms of documentation of the method of repair, use of delayed absorbable suture material for the repair of external anal sphincter and follow-up at 6 weeks to see the success of repair and plan the next delivery (p<0.05). The use of vacuum vaginal delivery increased to 27(19%) from 5(4%), but there was decrease in injuries complicated by instrumental vaginal deliveries (p<0.05). CONCLUSIONS: Despite the increase in the number of deliveries, the frequency of obstetric anal sphincter injuries remained similar to the previous audit, indicating that regular clinical audits are integral to keeping clinical practice in accordance with the established standards.


Assuntos
Lacerações , Complicações do Trabalho de Parto , Auditoria Clínica , Feminino , Humanos , Lacerações/epidemiologia , Lacerações/cirurgia , Complicações do Trabalho de Parto/epidemiologia , Complicações do Trabalho de Parto/cirurgia , Gravidez , Estudos Retrospectivos , Fatores de Risco
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 513-520, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096016

RESUMO

The use of whole exome sequencing (WES) for the detection of disease-causing variants of genetic diseases and for non-invasive prenatal screening (NIPS) of fetal aneuploidies are two major clinical applications of next generation sequencing (NGS). This article has summarized the official documents developed and updated by the American College of Medical Genetics and Genomics (ACMG) on governing WES and NIPS. These include the development of expert consensus policies and position statements on an ongoing basis to guide clinical application of NGS technology and variant analysis, establish evidence-based practical resources, as well as standards and guidelines to govern diagnosis and screening. These ACMG documents are valuable references to Chinese geneticists, but direct adoption of these standards and guidelines may not be practical due to the differences in disease-associated variant frequencies in Chinese population, socioeconomic status, and medical practice between the two countries. It is hoped that this review could facilitate the development of NGS and NIPS standards and guidelines that are consistent with international standards and concordant with medical genetics practice in China to provide high-quality, efficient and safe clinical services for patients and their families with genetic diseases.


Assuntos
Genômica , Sequenciamento de Nucleotídeos em Larga Escala , China , Consenso , Feminino , Humanos , Gravidez , Tecnologia , Estados Unidos
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 531-535, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096019

RESUMO

OBJECTIVE: To study the correlation between DNA methylation patterns and gene expression in Down syndrome (DS). METHODS: Induced pluripotent stem cells (iPSCs) derived from normal controls and DS patients were subjected to whole genome bisulfite sequencing and differentially methylated region (DMR) screening. Statistical analysis for chromosomal and gene element distribution were carried out for DMR. Gene ontology (GO) and enrichment-based cluster analysis were used to explore the molecular function of differentially expressed genes. RESULTS: A total of 1569 DMR were identified in iPSCs derived from DS patients, for which the proportion of hypermethylation in promoter regions was significantly greater than that of the genebody. No DMR enrichment was noted on chromosome 21. Hypermethylation of the promoter and genebody was predicted to be inhibitory for gene expression. Functional clustering revealed the pathways related to neurodevelopmental, stem cell pluripotency and organ size regulation to be significantly correlated with differentially methylated genes. CONCLUSION: Extensive and stochastic anomalies of genome-wide DNA methylation has been discovered in iPSCs derived from DS patients, for which the pattern and molecular regulation of methylation were significantly different from those of normal controls. Above findings suggested that DNA methylation pattern may play a vital role in both the pathogenesis of neurodevelopmental disorders and other phenotypic abnormalities during early embryonic development.


Assuntos
Síndrome de Down , Células-Tronco Pluripotentes Induzidas , Metilação de DNA , Síndrome de Down/genética , Feminino , Humanos , Gravidez , Regiões Promotoras Genéticas , Sequenciamento Completo do Genoma
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 541-544, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096021

RESUMO

OBJECTIVE: To explore the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with high risk signaled by non-invasive prenatal testing (NIPT). METHODS: From June 2017 to August 2019, 628 pregnant women with high risk signaled by NIPT underwent invasive prenatal diagnosis. Amniotic fluid or cord blood samples were subjected to chromosomal karyotyping analysis or CMA. Pregnancy outcome and postnatal conditions of the fetuses were followed up. RESULTS: The positive predictive value for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidy, other rare trisomies and copy number variants (CNVs) among the 628 women were 86.4% (127/147), 41.7% (30/72), 12.9% (4/31), 43.7% (101/231), 16.5% (14/85) and 52.2% (35/67), respectively. In 218 samples with normal karyotype, 5.5% (12/218) of additional pathogenic CNVs and 2.3% (5/218) of loss of heterozygosity were detected by CMA. CONCLUSION: CMA combined with karyotyping analysis can be used as first-tier test for prenatal diagnosis for women with high-risk signaled by NIPT.


Assuntos
Diagnóstico Pré-Natal , Feminino , Humanos , Cariotipagem , Análise em Microsséries , Gravidez , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 553-556, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096024

RESUMO

OBJECTIVE: To explore the genetic basis for a patient with tuberous sclerosis complex. METHODS: Genomic DNA was extracted from peripheral blood samples from members of his family and 100 unrelated healthy controls. The proband was subjected to next-generation sequencing, and candidate variant was confirmed by multiple ligation-dependent probe amplification (MLPA) and Sanger sequencing. Reverse transcription-PCR (RT-PCR) was carried out to determine the relative mRNA expression in the proband. RESULTS: The patient was found to harbor a c.2355+1G>C splicing variant of the TSC2 gene. Sequencing of cDNA confirmed that 62 bases have been inserted into the 3' end of exon 21, which has caused a frameshift producing a truncated protein. CONCLUSION: The novel splicing variant c.2355+1G>C of the TSC2 gene probably underlay the TSC in the proband. Above finding has expanded the variant spectrum of TSC2 and provided a basis for preimplantation genetic testing and/or prenatal diagnosis.


Assuntos
Esclerose Tuberosa , Feminino , Humanos , Mutação , Gravidez , Splicing de RNA/genética , Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 569-572, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096028

RESUMO

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) to verify a fetus with partial 18p deletion signaled by non-invasive prenatal testing. METHODS: G-banding chromosomal karyotyping analysis was carried out on amniotic fluid sample of the fetus and peripheral blood samples from the parents. Amniotic DNA was also subjected to CMA analysis. The fetus was also subjected to systematic ultrasound scan. RESULTS: The fetus was found to have a karyotype of 46,XX,18p+. CMA has revealed a 5 Mb deletion at 18p11.32-p11.31, a 2.9 Mb duplication at 18p11.31-p11.23, and a 2.5 Mb duplication at 18p11.23-p11.22. No chromosomal aberration or microdeletion/microduplication was detected in either parent. CONCLUSION: Non-invasive prenatal testing and CMA are both sensitive for the detection of chromosomal microdeletions and microduplications. CMA can help with clarification of genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.


Assuntos
Deleção Cromossômica , Diagnóstico Pré-Natal , Cromossomos , Feminino , Feto , Humanos , Cariotipagem , Gravidez
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 573-576, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096029

RESUMO

OBJECTIVE: To determine the chromosomal karyotype of a fetus with copy number variation (CNV) of the X chromosome signaled by non-invasive prenatal testing (NIPT). METHODS: NIPT was performed on the peripheral blood sample taken from the pregnant women. Amniotic fluid and cord blood samples were subjected to conventional G banded karyotyping, and were further analyzed by high-throughput sequencing for chromosome microdeletion/microduplication. The results were then verified by fluorescence in situ hybridization (FISH) on metaphase cells. RESULTS: The NIPT test of pregnant women suggested low risk for 21-trisomy, 18-trisomy, and 13-trisomy, whilst indicated the number of chromosome X to be low. The G banded karyotype of the amniotic fluid and cord blood cells was 46,XX. The result of high-throughput sequencing chromosome microdeletion/microduplication detection was seq[hg19](X)× 1, (Y)× 2. FISH showed a clear red signal at each end of a whole chromosome, and a green signal on the other chromosome, with a karyotype of 46,X,ish idic(Y) (q11.23) (SRY++, DXZ1+). C banding showed that there is a dense and a slightly loose centromere at both ends of the Y chromosome, and the parachromatin region was missing. The karyotype of amniotic fluid and cord blood cells was finally determined to be 46,X, pus idic(Y) (q11.23). CONCLUSION: For chromosome anomalies suggested by auxiliary report of NIPT, conventional karyotyping combined with high-throughput sequencing for chromosome microdeletion/microduplication should be adopted for the prevention and reduction of the rate of chromosome microdeletion/microduplication syndromes.


Assuntos
Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Aberrações Cromossômicas , Feminino , Humanos , Hibridização in Situ Fluorescente , Gravidez , Cromossomo X
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