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1.
J Neuroinflammation ; 20(1): 115, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37183260

RESUMEN

BACKGROUND: Microglial polarization is one of the most promising therapeutic targets for multiple central nervous system (CNS) disorders, including ischemic stroke. However, detailed transcriptional alteration of microglia following cerebral ischemic stroke remains largely unclear. METHODS: Focal cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) for 60 min in mice. Single-cell RNA sequencing (scRNA-seq) was performed using ischemic brain tissues from tMCAO and sham mice 3 days after surgery. Ch25h-/- mice were used to investigate the role of specific microglia subcluster on post-stroke infarct volume and neuroinflammation. RESULTS: We identified a relatively homeostatic subcluster with enhanced antigen processing and three "ischemic stroke associated microglia" (ISAM): MKI67+, CH25H+ and OASL+ subclusters. We found the MKI67+ subcluster undergo proliferation and differentiation into CH25H+ and OASL+ subclusters. CH25H+ microglia was a critical subcluster of ISAM that exhibited increased phagocytosis and neuroprotective property after stroke. Ch25h-/- mice developed significantly increased infarct volume following ischemic stroke compared to Ch25h+/-. Meanwhile, the OASL+ subcluster accumulated in the ischemic brain and was associated with the evolving of neuroinflammation after stroke, which was further aggravated in the aged mice brain. CONCLUSIONS: Our data reveal previously unrecognized roles of the newly defined CH25H+ and OASL+ microglia subclusters following ischemic stroke, with novel insights for precise microglia modulation towards stroke therapy.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratones , Animales , Microglía , Accidente Cerebrovascular Isquémico/complicaciones , Enfermedades Neuroinflamatorias , Accidente Cerebrovascular/complicaciones , Isquemia Encefálica/complicaciones , Infarto de la Arteria Cerebral Media/complicaciones , Ratones Endogámicos C57BL
2.
Hum Reprod ; 36(11): 2962-2974, 2021 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-34382079

RESUMEN

STUDY QUESTION: Can meteorological conditions modify the associations between NO2 and SO2 exposure and congenital limb defects (CLDs) during the first trimester of pregnancy? SUMMARY ANSWER: Increases in NO2 and SO2 exposure were consistently associated with higher risks of CLDs during the first trimester of pregnancy; both low- and high-temperature exposure and high air humidity act synergistically with the two air pollutants on CLDs. WHAT IS KNOWN ALREADY: Animal studies have indicated air pollutants are associated with CLDs, but corresponding epidemiological studies are limited with equivocal conclusions. Meteorological conditions are closely connected to the generation, diffusion, distribution and even chemical toxicity of air pollutants. STUDY DESIGN, SIZE, DURATION: This case-control study included 972 cases of CLDs and 9720 controls in Changsha, China during 2015-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cases from the hospital based monitoring system for birth defects (including polydactyly, syndactyly, limb shortening, and clubfoot) and healthy controls from the electronic medical records system were studied. Complete data on daily average NO2 and SO2 concentrations and meteorological variables were obtained from local monitoring stations to estimate monthly individual exposures during the first trimester of pregnancy, using the nearest monitoring station approach for NO2 and SO2 concentrations, and the city-wide average approach for temperature and relative humidity, respectively. The 25th and 75th percentiles of daily mean temperature, as well as the 50th percentile of daily mean relative humidity during the study period were used to classify high- and low-temperature exposure, and high humidity exposure based on existing evidence and local climate characteristics. Multivariate logistic regression models were used to estimate the independent effects per 10 µg/m3 increase in NO2 and SO2 on CLDs, and the attribute proportions of interaction (API) were used to quantify the additive joint effects of air pollutants with meteorological conditions after including a cross product interaction term in the regression models. MAIN RESULTS AND THE ROLE OF CHANCE: NO2 and SO2 exposures during the first trimester of pregnancy were consistently and positively associated with overall CLDs and subtypes, with adjusted odd ratios (aORs) ranging from 1.13 to 1.27 for NO2, and from 1.37 to 2.49 for SO2. The effect estimates were generally observed to be the strongest in the first month and then attenuated in the second and third months of pregnancy. Synergistic effects of both low and high temperature in combination with NO2 (with APIs ranging from 0.07 to 0.38) and SO2 (with APIs ranging from 0.18 to 0.51) appeared in the first trimester of pregnancy. Several significant modifying effects by high humidity were also observed, especially for SO2 (with APIs ranging from 0.13 to 0.38). Neither NO2 nor SO2 showed an interactive effect with season of conception. LIMITATIONS, REASONS FOR CAUTION: The methods used to estimate individual exposure levels of air pollutants and meteorological factors may lead to the misclassification bias because of the lack of information on maternal activity patterns and residential mobility during pregnancy. Moreover, we were unable to consider several potentially confounding factors, including socioeconomic status, maternal nutrient levels, alcohol use and smoking during early pregnancy due to unavailable data, although previous studies have suggested limited change to the results after when including these factors in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: The findings are helpful for understanding the combined effects of air pollution and meteorological conditions on birth defects. Environmental policies and practices should be formulated and implemented to decrease air pollutant emissions and improve meteorological conditions to reduce their harmful effects on pregnancy. Additionally, pregnant women should be suggested to reduce outdoor time when the air quality is poor, especially when ambient temperature is higher or lower than what is comfortable, or when it is excessively humid. STUDY FUNDING/COMPETING INTEREST(S): The study is funded by Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defects in Hunan Province (2019SK1012), Major Research and Development Projects in Hunan Province (2018SK2060) and Scientific and Technological Department Projects in Hunan Province (2017SK50802). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/análisis , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Dióxido de Nitrógeno/toxicidad , Embarazo , Dióxido de Azufre/análisis , Dióxido de Azufre/toxicidad
3.
BMC Oral Health ; 21(1): 530, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34654409

RESUMEN

BACKGROUND: A growing body of studies have investigated the association between air pollution exposure during early pregnancy and the risk of orofacial clefts, but these studies put more emphasis on particulate matter and reported inconsistent results, while research on the independent effects of gaseous air pollutants on orofacial clefts has been quite inadequate, especially in China. METHODS: A case-control study was conducted in Changsha, China from 2015 to 2018. A total of 446 cases and 4460 controls were included in the study. Daily concentrations of CO, NO2, SO2, O3, PM2.5 and PM10 during the first trimester of pregnancy were assigned to each subject using the nearest monitoring station method. Multivariate logistic regression models were applied to evaluate the associations of monthly average exposure to gaseous air pollutants with orofacial clefts and its subtypes before and after adjusting for particulate matter. Variance inflation factors (VIFs) were used to determine if the effects of gaseous air pollutants could be independent of particulate matter. RESULTS: Increase in CO, NO2 and SO2 significantly increased the risk of cleft lip with or without cleft palate (CL/P) in all months during the first trimester of pregnancy, with aORs ranging from 1.39 to 1.48, from 1.35 to 1.61 and from 1.22 to 1.35, respectively. The risk of cleft palate only (CPO) increased with increasing NO2 exposure levels in the first trimester of pregnancy, with aORs ranging from 1.60 to 1.66. These effects sustained and even exacerbated after adjusting for particulate matter. No significant effect of O3 was observed. CONCLUSIONS: Our study suggested that maternal exposure to CO, NO2, and SO2 during the first trimester of pregnancy might contribute to the development of orofacial clefts, and the associations were potentially independent of particulate matter.


Asunto(s)
Contaminantes Atmosféricos , Labio Leporino , Fisura del Paladar , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Estudios de Casos y Controles , China/epidemiología , Labio Leporino/inducido químicamente , Labio Leporino/epidemiología , Fisura del Paladar/inducido químicamente , Fisura del Paladar/epidemiología , Femenino , Gases , Humanos , Embarazo , Primer Trimestre del Embarazo
4.
World J Surg Oncol ; 14(1): 220, 2016 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-27549155

RESUMEN

BACKGROUND: Robot-assisted partial nephrectomy (RAPN) has been widely used worldwide, to determine whether RAPN is a safe and effective alternative to open partial nephrectomy (OPN) via the comparison of RANP and OPN. METHODS: A comprehensive literature search was performed within the databases including PubMed, Cochrane Library, and Embase updated on 30 September 2015. Summary data with their corresponding 95 % confidence intervals (CIs) were calculated using a random effects or fixed effects model. Heterogeneity and publication bias were also evaluated. RESULTS: A total of 16 comparative studies including 3024 cases were used for this meta-analysis. There are no significant differences in the demographic characteristic between the two groups, but the age was lower and the tumor size was smaller for the RAPN group. RAPN had a longer operative time and warm ischemia time but which showed less estimated blood loss, hospital stay, and perioperative complications. No differences existed in the margin status, the change of glomerular filtration rate, transfusion rate, and conversion rate between the two groups. There was no significant publication bias. CONCLUSIONS: RAPN offered a lower rate of perioperative complications, less estimated blood loss, and shorter length of hospital stay than OPN, suggesting that RAPN can be an effective alternative to OPN. Well-designed prospective randomized controlled trials will be helpful in validating our findings.


Asunto(s)
Neoplasias Renales/cirugía , Nefrectomía/métodos , Nefrectomía/estadística & datos numéricos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Transfusión de Componentes Sanguíneos/estadística & datos numéricos , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Conversión a Cirugía Abierta/estadística & datos numéricos , Tasa de Filtración Glomerular , Humanos , Tiempo de Internación/estadística & datos numéricos , Márgenes de Escisión , Nefrectomía/normas , Tempo Operativo , Resultado del Tratamiento , Isquemia Tibia/estadística & datos numéricos
5.
Biochem Biophys Res Commun ; 468(4): 666-70, 2015 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-26551459

RESUMEN

Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n = 3). Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P < 0.001). Chi-square test showed that expression of lncRNA-n336928 was positively correlated with bladder tumor stage and histological grade (P < 0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of lncRNA-n336928 had shorter overall survival time compared to the patients with low expression of lncRNA-n336928. Multivariate analysis indicated that lncRNA-n336928 was an independent prognostic factor for overall survival for bladder cancer patients. Collectively, our study shows that high expression of lncRNA-n336928 is associated with the progression of bladder cancer, and that lncRNA-n336928 might serve as a biomarker for prognosis of bladder cancer.


Asunto(s)
Biomarcadores de Tumor/genética , Predisposición Genética a la Enfermedad/genética , ARN Largo no Codificante/genética , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Distribución por Edad , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución por Sexo , Neoplasias de la Vejiga Urinaria/mortalidad
6.
J Immunol ; 190(11): 5559-66, 2013 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-23630348

RESUMEN

VH replacement provides a unique RAG-mediated recombination mechanism to edit nonfunctional IgH genes or IgH genes encoding self-reactive BCRs and contributes to the diversification of Ab repertoire in the mouse and human. Currently, it is not clear how VH replacement is regulated during early B lineage cell development. In this article, we show that cross-linking BCRs induces VH replacement in human EU12 µHC(+) cells and in the newly emigrated immature B cells purified from peripheral blood of healthy donors or tonsillar samples. BCR signaling-induced VH replacement is dependent on the activation of Syk and Src kinases but is inhibited by CD19 costimulation, presumably through activation of the PI3K pathway. These results show that VH replacement is regulated by BCR-mediated signaling in human immature B cells, which can be modulated by physiological and pharmacological treatments.


Asunto(s)
Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Células Precursoras de Linfocitos B/metabolismo , Receptores de Antígenos de Linfocitos B/genética , Receptores de Antígenos de Linfocitos B/metabolismo , Transducción de Señal , Antígenos CD19/metabolismo , Secuencia de Bases , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Línea Celular , Activación Enzimática , Reordenamiento Génico , Humanos , Cadenas Pesadas de Inmunoglobulina/química , Región Variable de Inmunoglobulina/química , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Datos de Secuencia Molecular , Tonsila Palatina/citología , Células Precursoras de Linfocitos B/citología , Proteínas Tirosina Quinasas/metabolismo , Quinasa Syk , Familia-src Quinasas/metabolismo
7.
Int J Mol Sci ; 15(11): 19330-41, 2014 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-25347272

RESUMEN

Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Here, we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer (adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09-0.81; p=0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10-2.91; p=0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (p>0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Future analyses will be conducted with more participants recruited in a case-control study.


Asunto(s)
Pueblo Asiatico/genética , Estudios de Asociación Genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Variación Genética , Neoplasias de la Vejiga Urinaria/genética , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , China , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/patología
8.
J Int Med Res ; 52(8): 3000605241274239, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39175229

RESUMEN

Bardet-Biedl syndrome is a rare autosomal recessive genetic disorder with heterogenous clinical manifestations. The present study reports the clinical features of a novel compound heterozygous genotype of the BBS2 gene in a 14-year-old girl and her 6-year-old sister who had complaints of early-onset low vision. Fundus images revealed retinitis pigmentosa-like changes, and full-field electroretinograms showed no amplitude for the rod or cone response in both patients. Interestingly, nystagmus was observed in the older sister. On physical examination, the sisters had moderate obesity without polydactyly, hypogonadism, or intellectual disability. Exome sequencing revealed a novel compound heterozygous genotype of BBS2 in the sisters, namely the paternally inherited NM_031885.5:c.534 + 1G > T variant and the maternally inherited NM_031885.5:c.700C > T (p.Arg234Ter) variant. Both variants were classified as pathogenic according to the American College of Medical Genetics and Genomics guidelines. This study provides useful information on the genotype-phenotype relationships of the BBS2 gene for genetic counseling and diagnosis.


Asunto(s)
Síndrome de Bardet-Biedl , Heterocigoto , Humanos , Femenino , Adolescente , Niño , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/diagnóstico , Genotipo , Secuenciación del Exoma , Linaje , Mutación , Fenotipo , Estudios de Asociación Genética , Electrorretinografía , Proteínas
9.
BMC Med Genomics ; 17(1): 230, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267058

RESUMEN

BACKGROUND: Spermatogenic failure is one of the leading causes of male infertility and its genetic etiology has not yet been fully understood. METHODS: The study screened a cohort of patients (n = 167) with primary male infertility in contrast to 210 normally fertile men using whole exome sequencing (WES). The expression analysis of the candidate genes based on public single cell sequencing data was performed using the R language Seurat package. RESULTS: No pathogenic copy number variations (CNVs) related to male infertility were identified using the the GATK-gCNV tool. Accordingly, variants of 17 known causative (five X-linked and twelve autosomal) genes, including ACTRT1, ADAD2, AR, BCORL1, CFAP47, CFAP54, DNAH17, DNAH6, DNAH7, DNAH8, DNAH9, FSIP2, MSH4, SLC9C1, TDRD9, TTC21A, and WNK3, were identified in 23 patients. Variants of 12 candidate (seven X-linked and five autosomal) genes were identified, among which CHTF18, DDB1, DNAH12, FANCB, GALNT3, OPHN1, SCML2, UPF3A, and ZMYM3 had altered fertility and semen characteristics in previously described knockout mouse models, whereas MAGEC1,RBMXL3, and ZNF185 were recurrently detected in patients with male factor infertility. The human testis single cell-sequencing database reveals that CHTF18, DDB1 and MAGEC1 are preferentially expressed in spermatogonial stem cells. DNAH12 and GALNT3 are found primarily in spermatocytes and early spermatids. UPF3A is present at a high level throughout spermatogenesis except in elongating spermatids. The testicular expression profiles of these candidate genes underlie their potential roles in spermatogenesis and the pathogenesis of male infertility. CONCLUSION: WES is an effective tool in the genetic diagnosis of primary male infertility. Our findings provide useful information on precise treatment, genetic counseling, and birth defect prevention for male factor infertility.


Asunto(s)
Secuenciación del Exoma , Infertilidad Masculina , Humanos , Masculino , Infertilidad Masculina/genética , Adulto , Variaciones en el Número de Copia de ADN
10.
Clin Case Rep ; 12(4): e8691, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38585583

RESUMEN

An encephalocele is a congenital malformation characterized by protrusion of the intracranial contents through a cranial defect. We report that a fetus of a pregnant mother who had two consecutive pregnancies with ultrasound-detected encephalocele carried compound heterozygous variants in B3GALNT2 NM_152490.5:c.[1423C > T (p.Gln475Ter)]; [261-2A > G] of maternal and paternal origins, respectively, as confirmed by exome sequencing followed by Sanger sequencing validation. The present case implies that mutations in B3GALNT2, a well-known dystroglycanopathy causative gene, may result in a phenotype of neural tube defect, providing new insights into the clinical spectrum of B3GALNT2-related disorders. Our study may contribute to prenatal screening/diagnosis and genetic counseling of congenital brain malformations.

11.
Cell Rep ; 43(3): 113963, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38492218

RESUMEN

T cell infiltration into white adipose tissue (WAT) drives obesity-induced adipose inflammation, but the mechanisms of obesity-induced T cell infiltration into WAT remain unclear. Our single-cell RNA sequencing reveals a significant impact of adipose stem cells (ASCs) on T cells. Transplanting ASCs from obese mice into WAT enhances T cell accumulation. C-C motif chemokine ligand 5 (CCL5) is upregulated in ASCs as early as 4 weeks of high-fat diet feeding, coinciding with the onset of T cell infiltration into WAT during obesity. ASCs and bone marrow transplantation experiments demonstrate that CCL5 from ASCs plays a crucial role in T cell accumulation during obesity. The production of CCL5 in ASCs is induced by tumor necrosis factor alpha via the nuclear factor κB pathway. Overall, our findings underscore the pivotal role of ASCs in regulating T cell accumulation in WAT during the early phases of obesity, emphasizing their importance in modulating adaptive immunity in obesity-induced adipose inflammation.


Asunto(s)
Tejido Adiposo , Linfocitos T , Ratones , Animales , Linfocitos T/metabolismo , Tejido Adiposo/metabolismo , Obesidad/metabolismo , Inflamación/patología , Células Madre/metabolismo
12.
Front Mol Neurosci ; 16: 1153156, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37187958

RESUMEN

Background: The endoplasmic reticulum-membrane protein complex (EMC) as a molecular chaperone is required for the proper synthesis, folding and traffic of several transmembrane proteins. Variants in the subunit 1 of EMC (EMC1) have been implicated in neurodevelopmental disorders. Methods: Whole exome sequencing (WES) with Sanger sequencing validation was performed for a Chinese family, including the proband (a 4-year-old girl who displayed global developmental delay, severe hypotonia and visual impairment), her affected younger sister and her non-consanguineous parents. RT-PCR assay and Sanger sequencing were used to detect abnormal RNA splicing. Results: Novel compound heterozygous variants in EMC1, including the maternally inherited chr1: 19566812_1956800delinsATTCTACTT[hg19];NM_015047.3:c.765_777delins ATTCTACTT;p.(Leu256fsTer10) and the paternally inherited chr1:19549890G> A[hg19];NM_015047.3:c.2376G>A;p.(Val792=) are identified in the proband and her affected sister. RT-PCR assay followed by Sanger sequencing reveals that the c.2376G>A variant leads to aberrant splicing, with retention of intron 19 (561bp) in the mature mRNA, which is presumed to introduce a premature translational termination codon (p.(Val792fsTer31)). Conclusion: Novel compound heterozygous variants in EMC1 have been identified in individuals with global developmental delay. Non-silent synonymous mutations should be kept in mind in genetic analysis.

13.
Front Endocrinol (Lausanne) ; 14: 1267946, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38075060

RESUMEN

Pseudoachondroplasia (PSACH) is a rare, dominant genetic disorder affecting bone and cartilage development, characterized by short-limb short stature, brachydactyly, loose joints, joint stiffness, and pain. The disorder is caused by mutations in the COMP gene, which encodes a protein that plays a role in the formation of collagen fibers. In this study, we present the clinical and genetic characteristics of PSACH in two Chinese families. Whole-exome sequencing (WES) analysis revealed two novel missense variants in the COMP gene: NM_000095.3: c.1319G>T (p.G440V, maternal) and NM_000095.3: c.1304A>T (p.D435V, paternal-mosaic). Strikingly, both the G440V and D435V mutations were located in the same T3 repeat motif and exhibited the potential to form hydrogen bonds with each other. Upon further analysis using Missense3D and PyMOL, we ascertained that these mutations showed the propensity to disrupt the protein structure of COMP, thus hampering its functioning. Our findings expand the existing knowledge of the genetic etiology underlying PSACH. The identification of new variants in the COMP gene can broaden the range of mutations linked with the condition. This information can contribute to the diagnosis and genetic counseling of patients with PSACH.


Asunto(s)
Acondroplasia , Proteína de la Matriz Oligomérica del Cartílago , Osteocondrodisplasias , Humanos , Acondroplasia/genética , Proteína de la Matriz Oligomérica del Cartílago/genética , Secuenciación del Exoma , Proteínas Matrilinas/genética , Osteocondrodisplasias/genética
14.
Front Pediatr ; 11: 1183388, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38027282

RESUMEN

Background: Wave In, which refers to the negativity between waves I and II in auditory brainstem response (ABR), is an electrophysiological phenomenon observed in previous studies. The term "high jugular bulb" (HJB) describes a jugular bulb that is located in a high position in the posterior aspect of the internal acoustic canal. The present study aimed to explore the correlation between wave In and the possibility of a HJB. Methods: This retrospective study included a cohort of pediatric patients diagnosed with profound hearing loss who were enrolled in a government-sponsored cochlear implantation program at an academic medical center between January 2019 and December 2022. The analysis involved examining the results obtained from the ABR test and high-resolution computed tomography (HRCT) of the temporal bone in the patients. The position of the jugular bulb was classified according to the Manjila and Semaan classification. Results: A total of 221 pediatric patients were included in the study. Twenty-four patients, with a median age of 3 years and a range of 1-7 years, showed significant bilateral (n = 21) or unilateral (n = 3) wave In (mean latency: right ear, 2.16 ms ± 0.22 ms; left ear, 2.20 ms ± 0.22 ms). The remaining 197 patients showed an absence of ABR. The HRCT images revealed that 18 of the 24 patients (75%) had HJB, but only 41 of the 197 patients who lacked ABR (20.8%) showed signs of HJB. The ratio difference was considered statistically significant based on the chi-squared test (χ2 = 32.10, p < 0.01). More than 50% of the HJBs were categorized as type 4 jugular bulbs, which are located above the inferior margin of the internal auditory canal. Conclusion: ABR wave In in pediatric patients with profound hearing loss suggests a high possibility of HJB. The physiological mechanism underlying this correlation needs further investigation.

15.
Front Med (Lausanne) ; 10: 1207248, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37521351

RESUMEN

Objective: To investigate the adverse pregnancy outcomes and associated risk factors among pregnant women with syphilis. Design: Pregnant women with syphilis in the registry for the prevention of mother-to-child transmission of AIDS, syphilis and hepatitis B in Hunan Province, China, from January 1, 2013 to December 31, 2018 were included in the study. Results: Among the 14,219 pregnant women with syphilis, 11,346 had definite pregnancy outcomes and were in singleton pregnancy. The risk factors related to adverse pregnancy outcomes include the age of pregnant women with syphilis <20 years old (aOR = 1.274, 95% CI: 1.088-1.493) or ≥ 35 years old (aOR = 1.402, 95% CI: 1.167-1.686), not married (aOR = 1.855, 95% CI: 1.453-2.367), initial syphilis detection in the late pregnancy (aOR = 1.266, 95% CI: 1.032-1.555), diagnosis of syphilis in the late pregnancy (aOR = 5.806, 95% CI: 1.796-18.770), diagnosis of syphilis during labor (aOR = 4.102, 95% CI: 1.263-13.330), husband/sexual partner infected with syphilis (aOR = 1.222, 95% CI: 1.068-1.398), untreated (aOR = 6.756, 95% CI: 5.586-8.197), and nonstandard medication (aOR = 3.300, 95% CI: 2.841-3.846). Conclusion: The prevalence of adverse pregnancy outcomes among pregnant women with syphilis in Hunan Province, China from 2013 to 2018 was relatively high. The adverse pregnancy outcomes associated with syphilis could be reduced by early detection and standard treatment of syphilis for pregnant women and their husbands/sexual partners.

16.
Cureus ; 15(1): e34208, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36843716

RESUMEN

BACKGROUND: Congenital cataract is a common cause of blindness in childhood. About half of the cases have a genetic etiology, and more than 100 genes have been associated with congenital cataracts. This study reports the clinical and genetic findings of a two-generation Chinese family affected by congenital cataract. METHODS: Ophthalmologic examinations were performed for clinical evaluation of the cataract patients. Whole exome sequencing (WES) and Sanger sequencing were used to identify potentially relevant mutations. The online programsProtein Variation Effect Analyzer (PROVEAN) and Sorting Intolerant from Tolerant (SIFT) were employed to predict the impact of variation on protein function. RESULTS: Both the proband and her mother were blind because of bilateral nuclear cataracts, and the elder brother of the proband also manifested obvious bilateral cataracts. Sanger sequencing confirmed the mutations in the proband as well as in her mother. The elder brother simply carried the PAX6 c.221G>A variation. The WFS1 c.2070_2079del variation potentially generates a loss-of-function mutant. CONCLUSION: The novel PAX6mutation (c.221G>A) is associated with congenital cataract, and the WFS1 mutation (c.2070_2079del) may interactively aggravates this process. These findings may increase our understanding of the genetic etiology of congenital cataract.

17.
BMC Med Genomics ; 16(1): 318, 2023 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-38062428

RESUMEN

BACKGROUND: Short-rib polydactyly syndrome (SRPS) refers to a group of lethal skeletal dysplasias that can be difficult to differentiate between subtypes or from other non-lethal skeletal dysplasias such as Ellis-van Creveld syndrome and Jeune syndrome in a prenatal setting. We report the ultrasound and genetic findings of four unrelated fetuses with skeletal dysplasias. METHODS: Systemic prenatal ultrasound examination was performed in the second or third trimester. Genetic tests including GTG-banding, single nucleotide polymorphism (SNP) array and exome sequencing were performed with amniocytes or aborted fetal tissues. RESULTS: The major and common ultrasound anomalies for the four unrelated fetuses included short long bones of the limbs and narrow thorax. No chromosomal abnormalities and pathogenic copy number variations were detected. Exome sequencing revealed three novel variants in the DYNC2H1 gene, namely NM_001080463.2:c.6809G > A p.(Arg2270Gln), NM_001080463.2:3133C > T p.(Gln1045Ter), and NM_001080463.2:c.337C > T p.(Arg113Trp); one novel variant in the IFT172 gene, NM_015662.3:4540-5 T > A; and one novel variant in the WDR19 gene, NM_025132.4:c.2596G > C p.(Gly866Arg). The genotypes of DYNC2H1, IFT172 and WDR19 and the phenotypes of the fetuses give hints for the diagnosis of short-rib thoracic dysplasia (SRTD) with or without polydactyly 3, 10, and 5, respectively. CONCLUSION: Our findings expand the mutation spectrum of DYNC2H1, IFT172 and WDR19 associated with skeletal ciliopathies, and provide useful information for prenatal diagnosis and genetic counseling on rare skeletal disorders.


Asunto(s)
Ciliopatías , Síndrome de Ellis-Van Creveld , Osteocondrodisplasias , Polidactilia , Embarazo , Femenino , Humanos , Variaciones en el Número de Copia de ADN , Síndrome de Ellis-Van Creveld/diagnóstico por imagen , Síndrome de Ellis-Van Creveld/genética , Diagnóstico Prenatal , Ciliopatías/diagnóstico por imagen , Ciliopatías/genética , Proteínas del Citoesqueleto/genética , Proteínas Adaptadoras Transductoras de Señales/genética
18.
Stem Cell Res Ther ; 14(1): 336, 2023 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-37981699

RESUMEN

BACKGROUND: Kidney organoids derived from human pluripotent stem cells (HiPSCs) hold huge applications for drug screening, disease modeling, and cell transplanting therapy. However, these applications are limited since kidney organoid cannot maintain complete morphology and function like human kidney. Kidney organoids are not well differentiated since the core of the organoid lacked oxygen, nutrition, and vasculature, which creates essential niches. Hypoxia-inducible factor-1 α (HIF-1α) serves as a critical regulator in vascularization and cell survival under hypoxia environment. Less is known about the role of HIF-1α in kidney organoids in this regard. This study tried to investigate the effect of HIF-1α in kidney organoid vascularization and related disease modeling. METHODS: For the vascularization study, kidney organoids were generated from human induced pluripotent stem cells. We overexpressed HIF-1α via plasmid transfection or treated DMOG (Dimethyloxallyl Glycine, an agent for HIF-1α stabilization and accumulation) in kidney progenitor cells to detect the endothelium. For the disease modeling study, we treated kidney organoid with cisplatin under hypoxia environment, with additional HIF-1α transfection. RESULT: HIF-1α overexpression elicited kidney organoid vascularization. The endothelial cells and angiotool analysis parameters were increased in HIF-1α plasmid-transfected and DMOG-treated organoids. These angiogenesis processes were partially blocked by VEGFR inhibitors, semaxanib or axitinib. Cisplatin-induced kidney injury (Cleaved caspase 3) was protected by HIF-1α through the upregulation of CD31 and SOD2. CONCLUSION: We demonstrated that HIF-1α elicited the process of kidney organoid vascularization and protected against cisplatin-induced kidney organoid injury in hypoxia environment.


Asunto(s)
Angiogénesis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Riñón , Modelos Biológicos , Organoides , Organoides/irrigación sanguínea , Organoides/metabolismo , Riñón/metabolismo , Células Madre Multipotentes , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Humanos , Plásmidos/genética , Expresión Génica , Células Madre/citología , Células Madre/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de la Angiogénesis/farmacología , Angiogénesis/efectos de los fármacos , Angiogénesis/fisiopatología , Axitinib/farmacología , Células Cultivadas , Cisplatino/farmacología , Hipoxia de la Célula , Enfermedades Renales/fisiopatología
19.
Front Genet ; 13: 1014188, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36246610

RESUMEN

Background: Geleophysic dysplasia and Weill-Marchesani syndrome from the acromelic dysplasias group of genetic skeletal disorders share remarkable clinical and genetic overlap. Methods: Ophthalmological, physical, radiological examinations were conducted with a female patient in her early 30 s. Whole exome sequencing followed by Sanger sequencing validation was performed to identify the genetic cause. Results: The patient, born to consanguineous Chinese parents, presented with microspherophakia, lens subluxation, high myopia, short statue, small hands and feet, stiff joints, and thickened skin. A diagnosis of Weill-Marchesani syndrome was initially made for her. However, genetic testing reveals that the patient is homozygous for the c.1966G>A (p.Gly656Ser) variant in ADAMTSL2, and that the patient's healthy mother and daughter are heterozygous for the variant. As mutations in ADAMTSL2 are known to cause autosomal recessive geleophysic dysplasia, the patient is re-diagnosed with geleophysic dysplasia in terms of her genotype and phenotype. Conclusion: The present study describes the clinical phenotype of the homozygous ADAMTSL2 p. Gly656Ser variant, which increases our understanding of the genotype-phenotype correlation in acromelic dysplasias.

20.
Reprod Toxicol ; 104: 106-113, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34311057

RESUMEN

Accumulating studies have been focused on the independent effects of air pollutants and ambient heat exposure on congenital heart defects (CHDs) but with inconsistent results, and their interactive effect remains unclear. A case-control study including 921 cases and 9210 controls was conducted in Changsha, China in warm season in 2015-2018. The gravidas were assigned monthly averages of daily air pollutants and daily maximum temperature using the nearest monitoring station method and city-wide average method, respectively, during the first trimester of pregnancy. Multivariate logistic regression models were used to estimate the independent effects of each air pollutant and different ambient heat exposure indicators. Their additive joint effects were quantified using attribute proportions of interaction (API). Increasing SO2 consistently increased the risk of CHDs in the first trimester of pregnancy, with aORs ranging from 1.78 to 2.04. CO, NO2 and PM2.5 exposure in the first month of pregnancy, and O3 exposure in the second and third month of pregnancy were also associated with elevated risks of CHDs, with aORs ranging from 1.04 to 1.15. Depending on the ambient heat exposure indicator used, air pollutants showed more apparent synergistic effects (API > 0) with less and moderately intense heat exposure. Maternal exposure to CO, NO2, SO2, PM2.5 and O3 during early pregnancy increased risk of CHDs, and ambient heat exposure may enhance these effects. Our findings help to understand the interactive effect of air pollution with ambient heat exposure on CHDs, which is of vital public health significance.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/estadística & datos numéricos , Cardiopatías Congénitas/epidemiología , Calor , Estudios de Casos y Controles , China , Femenino , Humanos , Modelos Logísticos , Exposición Materna/estadística & datos numéricos , Material Particulado/toxicidad , Embarazo , Primer Trimestre del Embarazo
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