Glossopharyngeal neuralgia (GPN) refers to paroxysmal severe pain located to glossopharyngeal part or ear, which is a rare clinical event. In this report, we describe a patient suffered from glossopharyngeal neuralgia...Glossopharyngeal neuralgia (GPN) refers to paroxysmal severe pain located to glossopharyngeal part or ear, which is a rare clinical event. In this report, we describe a patient suffered from glossopharyngeal neuralgia due to vertebrobasilar dolichoectasia (VBD). A 72-year-old Chinese male was referred to our clinic with a complaint of paroxysmal severe pain in the right external auditory canal and auricle since 1 month, which could be precipitated by feed and accompanied with the vagus nerve irritation (bradycardia, low blood pressure, syncope) sometimes. Both computed tomographic angiography and digital subtraction angiography demonstrated a VBD (maximum diameter 5.7 mm) and a large fusiform aneurysm of basilar artery (maximum diameter 13.8 mm). The diagnosis is established on clinical and radiological signs. This is the first report of this kind in the literature. Although a few cases demonstrate that VBD can cause GPN, it should be considered as a possible etiology in patients with GPN.展开更多
The authors regret having an image assembly error in Figure 5Ca,in which the image for the "Oh dBiFP-AdRFp"group was erroneously duplicated with an overlapping image from the"36h BiFP dBIFP-AdR-simH19&q...The authors regret having an image assembly error in Figure 5Ca,in which the image for the "Oh dBiFP-AdRFp"group was erroneously duplicated with an overlapping image from the"36h BiFP dBIFP-AdR-simH19"group.We confirm the error is restricted to the image assembly,and the underlying data and conclusions are correct and unchanged.The authors would like to apologize for any inconvenience caused.展开更多
The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"gro...The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"group;and the image for"AdsimB9-1+BMP9"groupwas erroneouslyduplicatedwithan overlapping image from"AdsimB9-8+BMP9"group.In Figure 4Apanel a,the images for"BMP9"group and "BMP9+simB9-4"group were erroneously duplicated with an overlapping image from"simB9-4"group.In Figure 5A,the image for"BMP9+simB9-4/Day3"group was erroneously duplicated with an overlapping image from"BMP9+simB9-7/Day3"group;and the image for"BMP9+simB9-4/Day5"group was erroneously duplicated with an overlapping image from an unrelated experiment.In Figure 6B,the image for"BMP9+simB9-7/Day 11"group was erroneously duplicated with an overlapping image from the"BMP9+simB9-4/Day 11"group.展开更多
Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the mo...Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.展开更多
While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs)...While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs),which are critical components of epigenetic regulation.lncRNAs are emerging as critical regulators of gene expression and genomic stability.However,it remains largely unknown about how lncRNAs are regulated.Here,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncRNA transcript levels in a high throughput fashion.Specifically,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP protein.We further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncRNA H19 chimeric transcript is silenced by mouse H19-specific siRNAs.Therefore,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncRNAs by microRNAs,synthetic regulatory RNA molecules,RNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders.展开更多
文摘Glossopharyngeal neuralgia (GPN) refers to paroxysmal severe pain located to glossopharyngeal part or ear, which is a rare clinical event. In this report, we describe a patient suffered from glossopharyngeal neuralgia due to vertebrobasilar dolichoectasia (VBD). A 72-year-old Chinese male was referred to our clinic with a complaint of paroxysmal severe pain in the right external auditory canal and auricle since 1 month, which could be precipitated by feed and accompanied with the vagus nerve irritation (bradycardia, low blood pressure, syncope) sometimes. Both computed tomographic angiography and digital subtraction angiography demonstrated a VBD (maximum diameter 5.7 mm) and a large fusiform aneurysm of basilar artery (maximum diameter 13.8 mm). The diagnosis is established on clinical and radiological signs. This is the first report of this kind in the literature. Although a few cases demonstrate that VBD can cause GPN, it should be considered as a possible etiology in patients with GPN.
文摘The authors regret having an image assembly error in Figure 5Ca,in which the image for the "Oh dBiFP-AdRFp"group was erroneously duplicated with an overlapping image from the"36h BiFP dBIFP-AdR-simH19"group.We confirm the error is restricted to the image assembly,and the underlying data and conclusions are correct and unchanged.The authors would like to apologize for any inconvenience caused.
文摘The authors regret having several image assembly errors.Specifically,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"group;and the image for"AdsimB9-1+BMP9"groupwas erroneouslyduplicatedwithan overlapping image from"AdsimB9-8+BMP9"group.In Figure 4Apanel a,the images for"BMP9"group and "BMP9+simB9-4"group were erroneously duplicated with an overlapping image from"simB9-4"group.In Figure 5A,the image for"BMP9+simB9-4/Day3"group was erroneously duplicated with an overlapping image from"BMP9+simB9-7/Day3"group;and the image for"BMP9+simB9-4/Day5"group was erroneously duplicated with an overlapping image from an unrelated experiment.In Figure 6B,the image for"BMP9+simB9-7/Day 11"group was erroneously duplicated with an overlapping image from the"BMP9+simB9-4/Day 11"group.
基金The reported work was supported in part by research grants from the National Institutes of Health(CA226303,DE020140 to TCH and RRR)the U.S.Department of Defense(OR130096 to JMW)+1 种基金the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust(RRR,TCH),the Scoliosis Research Society(TCH and MJL)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906 to TCH).
文摘Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.
基金The reported work was supported in part by research grants from the National Institutes of Health(AT004418,DE020140 to TCH and RRR)the US Department of Defense(OR130096 to JMW)+5 种基金the Scoliosis Research Society(TCH and MJL)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906 to TCH)the National Natural Science Foundation of China(#81201916 to XW)ZZ was a recipient of protectorate fellowship from China Scholarship CouncilThis project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430.
文摘While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs),which are critical components of epigenetic regulation.lncRNAs are emerging as critical regulators of gene expression and genomic stability.However,it remains largely unknown about how lncRNAs are regulated.Here,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncRNA transcript levels in a high throughput fashion.Specifically,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP protein.We further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncRNA H19 chimeric transcript is silenced by mouse H19-specific siRNAs.Therefore,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncRNAs by microRNAs,synthetic regulatory RNA molecules,RNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders.
