Objective To assess the value of non-invasive prenatal testing based on cfDNA barcode-enabled single-molecule test (cfBEST) for the prenatal diagnosis of oculocutaneous albinism type I in a family. Methods Prenatal genetic diagnosis was carried out by using the cfBEST-based method as well as invasive prenatal diagnosis through amniocentesis. The outcome of the pregnancy was followed up. Results Non-invasive prenatal testing based on cfBEST showed a fetal DNA concentration of 6.6%, with the proportion of c.929_930insC (p.Arg311Lysfs*7) and c.1037-7T>A mutations being 45.7% and 0%, respectively. The posterior frequency of the negative results was 1, suggesting that the fetus carried neither of the two mutations. The result was consistent with that of invasive prenatal diagnosis, and the follow-up found that the fetus was normal. Conclusion Non-invasive prenatal testing based on cfBEST can be used to detect maternal and fetal genotypes in maternal cell-free DNA, which is clinically feasible.
Abstract Background and objectives: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a poor prognosis. Long noncoding RNAs (lncRNAs) are now considered as key gene expression regulators and play important roles in different types of cancer. This study aimed to identify potential lncRNAs and uncover vital molecular mechanisms guiding clinical therapy for HCC. Methods Based on four microarray datasets (GSE112613, GSE84004, GSE67260, and GSE101728) from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database of lncRNAs expression in patients with HCC, quantitative real-time PCR (qRT-PCR), cell transfection, cell proliferation assay, scratch wound healing, transcriptome sequencing, and immunofluorescence assays were used to analyze the clinical value and molecular mechanism of LINC02362 in HCC. Results High LINC02362 expression was positively correlated with longer overall survival (OS) and exhibited excellent diagnostic accuracy, suggesting that LINC02362 may inhibit HCC progression. Increased LINC02362 expression in HCC cell lines (Hep 3B and Huh 7) after lentiviral infection, overexpression of LINC02362 inhibits hepatocellular carcinoma cell proliferation, migration and invasion and then transcriptome sequencing was performed. Potential molecular LINC02362 pathways in HCC were determined using ClusterProfiler R package in enrichment analyses. Protein–protein interaction networks (PPI) were used to screen hub genes. PPI networks and OS data confirmed that EFNA5 was a downstream target positively regulated by LINC02362. Conclusions The LINC02362–EFNA5 axis appears to inhibit HCC progression; thus, it can be used to diagnose, prognose, and treat HCC.
Transcription factors of the SoxD protein family have previously been shown to prevent precocious specification and terminal differentiation of oligodendrocyte progenitor cells in the developing spinal cord. Using mice with specific deletion of the SoxD proteins Sox5 and Sox6 in the central nervous system, we now show that SoxD proteins additionally influence migration of oligodendrocyte progenitors in the spinal cord as well as in the forebrain. In mutant mice, emigration of oligodendrocyte progenitors from the ventricular zone and colonization of the mantle zone are significantly delayed probably because of reduced expression of Pdgf receptor alpha and decreased responsiveness toward Pdgf‐A as a main migratory cue. In addition to this direct cell‐autonomous effect on Pdgf receptor alpha expression, SoxD proteins furthermore promote oligodendroglial migration by keeping the cells in an undifferentiated state and preventing a premature loss of their migratory capacity. This indirect effect becomes particularly important during late embryonic and early postnatal phases of oligodendroglial development. Finally, we show that Sox5 and Sox6 cooperate with Sox9 and Sox10 to activate Pdgf receptor alpha expression and thereby maintain oligodendrocyte progenitors in the immature state. This contrasts with their behavior on myelin genes where they antagonize the function of SoxE proteins. It argues that SoxD proteins can function either as repressors or as co‐activators of SoxE proteins thereby modulating their function in a stage‐specific manner. GLIA 2016;64:122–138
Abstract Background: Hereditary retinopathy is a significant cause of blindness worldwide. Despite the discovery of many mutations in various retinopathies, a large part of patients remain undiagnosed genetically. Targeted next generation sequencing of the human genome is a suitable approach for retinopathy molecular diagnosis. Methods: We described a cohort of 211 families from central China with various forms of retinopathy, 95 families of which were investigated using NGS multi-gene panel sequencing as well as the other 116 patients were LHON suspected tested by Sanger sequencing. We validated the candidate variants by PCR-based Sanger sequencing. We have made comprehensive analysis of the cases through sequencing data and ophthalmologic examination information. Results: The potentially causal mutation was identified in majority of the families with retinopathy (57.9% of 95 families) and Leber hereditary optic neuropathy (LHON) (21.6% of 116 families). The identified mutations (68mutations, 37 of which are novel) of the 95 families spanned 31 known disease genes, about half have not been reported relation to hereditary retinopathy. The NGS panel solution provides 45.3% potential diagnostic rate of the retinopathy families and another 12.6% families detect candidate gene mutations with undefined pathogenicity in this study. Conclusion: Our study showed novel mutations and phenotypic aspects of retinopathy, and demonstrated genetic and clinical heterogeneity of the conditions. Our results illustrated the significance of molecular genetic testing for patients with hereditary retinopathy.
Objective
To explore the effect of 1,25-dihydroxy vitamin D3 (VD) on the expression of C-Jun N-terminal kinase/C-Jun (JNK/C-Jun) inflammatory pathway in the liver of type 2 diabetes mellitus (T2DM) rats and the possible mechanisms.
Methods
Sprague Dawley(SD) rats were divided into normal control group(NC), T2DM group(DM) and calcitriol-treated group(VD) via random number table. Calcitriol was given to VD group by gavage for 8 weeks, while the DM and NC group received peanut oil. After sacrifice, body weight was measured and fasting blood glucose(FBG), alanine transaminase(ALT), asparate transaminase(AST), total cholesterol(TC), triacylglycerol(TG) in serum were tested. Liver histopathology was examined by hematoxylin-eosin (HE) staining. The mRNA levels of JNK, C-Jun and its downstream cytokines tumor necrosis factor(TNF-α) and interleukin(IL-1β) were measured by real-time fluorescence quantitative PCR. The protein expression was analyzed by immunohistochemical staining and Western blotting.The t test was performed for pair-wise comparison and wilcoxon rank sum test was used for ranked data.
Results
The level of FBG, ALT, AST, TC and TG in DM group increased and body weight decreased compared with those in NC group((25.7±2.3)vs(5.8±0.9) mmol/L, (137±12)vs(53±6)U/L,(162±13)vs(65±7)U/L, (1.4±0.2)vs(1.21±0.08)mmol/L, (1.32±0.15)vs(0.73±0.10)mmol/L,(362±12)vs(452±16) g; t=29.573,26.142,14.395, 10.632,11.746,9.539, respectively, all P<0.05). Compared with DM group, ALT,AST and TG decreased significantly in VD group((112±10)vs(137±12) U/L, (129±11)vs (162±13) U/L, (1.06±0.14)vs (1.32±0.15) mmol/L; t=5.382,6.043,5.268, all P<0.05). HE staining showed that liver cells were in alignment and normal in NC group, whereas appeared swelling and fatty degeneration with inflammatory cells infiltration in DM group. VD treatment could alleviate the pathologic changes. The mRNA and protein levels of JNK, C-Jun, TNF-α and IL-1β in DM group increased compared with those in NC group, VD treatment down-regulated this inflammatory factors compared with DM group(χ2=19.958, 20.710, 20.969, 21.255, respectively, all P<0.05). JNK was positive correlated significantly with C-Jun, TNF-α, IL-1β (r=0.857,0.821,0.836,P<0.05).
Conclusion
1,25(OH)2D3 may protect diabetes-induced liver complications by down-regulating the inflammatory pathway of JNK/C-Jun.
Key words:
Calcitriol; Diabetes Mellitus,type 2; Liver; Inflammation
To explore the genetic etiology of a Chinese pedigree affected with infantile hepatitis syndrome.Genes associated with liver diseases subjected to high-throughput sequencing. Candidate variants were validated by Sanger sequencing of the proband and his parents. The pathogenicity of the variants was analyzed through bioinformatic analysis.High-throughput sequencing revealed that the proband has harbored c.182T>C (p.F61S) and c.293C>T (p.P98L) variants of the MPV17 gene, which were verified by Sanger sequencing to be inherited from his parents. The variant c.182T>C (p.F61S) was unreported previously and predicted to be likely pathogenic by bioinformatic analysis.The proband was caused by the compound heterozygous variations of MPV17 gene including c.182T>C (p.F61S) and c.293C>T (p.P98L). Discovery of the novel variant has enriched the spectrum of pathogenic variants of the MPV17 gene.
Eight new species presented are Calostoma areolatum collected in Wuyishan National Park (China), Crinipellis bidens from Hubei Province (China), Lactifluus sainii from Himalayan India, Inocybe elata from Yunnan (China), Inocybe himalayensis from Pakistan. Specimens previously identified as Massalongia carnosa represent a new species, namely M. patagonica restricted to southern South America. Saprolegnia maragheica is a new oomycete species of fresh water in Maraghe (Iran). Uncispora wuzhishanensis is a new aquatic hyphomycete species. A type specimen of Raddetes turkestanicus was studied and based on this the new combination Conocybe turkestanica, is proposed. Argyranthemum frutescens is a new host for Alternaria alternata and Syzygium cumini for Phyllosticta capitalensis in India. Crepidotus ehrendorferi is confirmed for Hungary and Pluteus leucoborealis for Central Europe, and for the phytogeographical region of Carpaticum. Pseudopithomyces palmicola is shown to occur on grapevine and it is validated by adding a unique identifier. Terfezia fanfani is reported first from Algeria.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)