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《Genetics in medicine》2023,25(11):100922
PurposeRPH3A encodes a protein involved in the stabilization of GluN2A subunit of N-methyl-D-aspartate (NMDA)-type glutamate receptors at the cell surface, forming a complex essential for synaptic plasticity and cognition. We investigated the effect of variants in RPH3A in patients with neurodevelopmental disorders.MethodsBy using trio-based exome sequencing, GeneMatcher, and screening of 100,000 Genomes Project data, we identified 6 heterozygous variants in RPH3A. In silico and in vitro models, including rat hippocampal neuronal cultures, have been used to characterize the effect of the variants.ResultsFour cases had a neurodevelopmental disorder with untreatable epileptic seizures [p.(Gln73His)dn; p.(Arg209Lys); p.(Thr450Ser)dn; p.(Gln508His)], and 2 cases [p.(Arg235Ser); p.(Asn618Ser)dn] showed high-functioning autism spectrum disorder. Using neuronal cultures, we demonstrated that p.(Thr450Ser) and p.(Asn618Ser) reduce the synaptic localization of GluN2A; p.(Thr450Ser) also increased the surface levels of GluN2A. Electrophysiological recordings showed increased GluN2A-dependent NMDA ionotropic glutamate receptor currents for both variants and alteration of postsynaptic calcium levels. Finally, expression of the Rph3AThr450Ser variant in neurons affected dendritic spine morphology.ConclusionOverall, we provide evidence that missense gain-of-function variants in RPH3A increase GluN2A-containing NMDA ionotropic glutamate receptors at extrasynaptic sites, altering synaptic function and leading to a clinically variable neurodevelopmental presentation ranging from untreatable epilepsy to autism spectrum disorder. 相似文献
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《Complementary therapies in clinical practice》2014,20(1):48-53
Long-term care (LTC) facilities house individuals with diverse combinations of cognitive and physical impairments, and the practice of Seated Qigong eliminates common exercise barriers. This study hypothesized: 1) a single session would lower blood pressure (BP) and improve quality of life (QOL) in a generalized LTC population, and 2) these responses would be attenuated with chronic (weekly) Seated Qigong practice. Ten residents (6 female; 86 ± 7 years) participated in 1X/week Seated Qigong sessions for 10-weeks. BP and QOL were assessed pre- and post-session at baseline and following 5- and 10-weeks of Qigong. Systolic BP was significantly reduced immediately post-session after 10-weeks of Qigong (P = 0.03), yet unchanged at baseline and after 5-weeks (all P > 0.05). Diastolic BP and QOL remained unchanged (P > 0.05). A session of Seated Qigong elicits a hypotensive response with exposure, supporting the notion that repeated sessions may provide advantageous health benefits. 相似文献
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BackgroundNon-small cell lung cancer (NSCLC) chemoresistance usually limits the clinical efficacy of chemotherapeutic approaches. However, few reports have revealed the regulation of miR-135b and Frizzled-1 (FZD1) involved in NSCLC chemoresistance.MethodsTo identify the mechanism of miR-135b and FZD1 in NSCLC chemoresistance and to observe their biological functions, we detected the expression levels of miR-135b and FZD1 by conducting quantitative real-time polymerase chain reaction (RT-qPCR) and modified the expressions of miR-135b and FZD1 by transiently transfecting cells with miR-135b mimics or FZD1-siRNA. The 3′-untranslated region (3′-UTR) of FZD1 combined with miR-135b was verified through dual-luciferase reporter assay.ResultsCompared with that in A549 parental cell lines, the miR-135b expression in drug-resistant lung cancer cell lines (A549/DDP) was decreased and their FZD1 expression was increased. The increased miR-135b expression and silenced FZD1 expression enhanced the sensitivity of resistant cells to cisplatin treatment. The high expression of miR-135b in A549/DDP cells remarkably decreased the mRNA levels of FZD1. FZD1 was further identified as the functional downstream target of miR-135b by directly targeting the 3′-UTR of FZD1.ConclusionThe amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation. 相似文献
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Wen Wang Dazhi Fan Jun Wang Shuzhen Wu Ying Lu Yunying He 《Hypertension in pregnancy》2018,37(3):168-174
Objective: Previous studies have reported a positive association between hypertensive disorders complicating pregnancy and placenta accreta. However, whether hypertensive disorders complicating pregnancy associated with placenta accreta is still not clear. The objective was to systematically review the literature to determine a possible association between hypertensive disorders complicating pregnancy and placenta accreta. Methods: A systematic search of PubMed database, the Cochrane Library, Willy Online Library, and ScienceDirect database through 1st December 2015, was conducted. Two authors independently assessed data extraction and quality of the studies using the Newcastle-Ottawa Scale. Assessment of heterogeneity and analysis of data were operated by Review Manager 5.3.0. Results: Three studies involving 4174 patients who developed hypertensive disorders complicating pregnancy of a total of 38,004 pregnant women were selected. The result of our meta-analysis revealed that pregnancy induced hypertension was significantly associated with a reduction of placenta accreta (OR = 0.50, 95% CI: 0.30–0.82; heterogeneity: I2 = 13%, p = 0.32). Conclusions: Our meta-analysis demonstrated that the risk of placenta accreta is reduced in women with hypertensive disorders complicating pregnancy. Further well-designed studies are warranted to testify the result and explored any potential mechanism association between hypertensive disorders complicating pregnancy and placenta accreta. 相似文献