BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a rare autoimmune disorder.The symptoms of anti-NMDAR encephalitis include behavioral problems,speech problems,psychosis,seizures,and memory def...BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a rare autoimmune disorder.The symptoms of anti-NMDAR encephalitis include behavioral problems,speech problems,psychosis,seizures,and memory deficits,among others.However,laryngospasm is rare.We present the case of a patient with anti-NMDAR antibodies and severe laryngospasms.CASE SUMMARY The patient was a 15-year-old female with normal psychomotor development.She was initially admitted to our neurological intensive care unit with seizures.She received anti-epilepsy treatment,and the seizures disappeared.However,2 wk later,she developed behavioral problems and speech impairment.Then,she developed severe laryngospasms,which were treated with intubation and a tracheotomy.Antibodies against the NMDAR were detected in the patient’s cerebrospinal fluid.Therefore,she was diagnosed with anti-NMDAR encephalitis.In addition,she received intravenously administered immunoglobulins,and methylprednisolone was administered.The patient’s symptoms gradually improved,and she was discharged from our hospital.Approximately 9 mo later,the patient could speak sentences,walk independently,and carry out activities of daily living independently.Through our case report,we highlighted laryngospasm as an uncommon presentation in patients with anti-NMDAR encephalitis.CONCLUSION Laryngospasm may be an uncommon clinical manifestation of anti-NMDAR encephalitis.展开更多
AIM: To investigate the role of Gadd45 a in hepatic fibrosis and the transforming growth factor(TGF)-β/Smad signaling pathway.METHODS: Wild-type male BALB/c mice were treated with CCl_4 to induce a model of chronic l...AIM: To investigate the role of Gadd45 a in hepatic fibrosis and the transforming growth factor(TGF)-β/Smad signaling pathway.METHODS: Wild-type male BALB/c mice were treated with CCl_4 to induce a model of chronic liver injury. Hepatic stellate cells(HSCs) were isolated from the liver of BALB/c mice and were treated with small interfering RNAs(si RNAs) targeting Gadd45 a or the pc DNA3.1-Gadd45 a recombinant plasmid. Cellular α-smooth muscle actin(α-SMA), β-actin, type Ⅰ collagen, phosphoSmad2, phospho-Smad3, Smad2, Smad3, and Smad4 were detected by Western blots. The m RNA levels of α-SMA, β-actin, and type Ⅰ collagen were determined by quantitative real-time(q RT)-PCR analyses. Reactive oxygen species production was monitored by flow cytometry using 2,7-dichlorodihydrofluorescein diacetate.Gadd45a, Gadd45 b, anti-Gadd45 g, type Ⅰ collagen, and SMA local expression in liver tissue were measured by histologic and immunohistochemical analyses. RESULTS: Significant downregulation of Gadd45 a, but not Gadd45 b or Gadd45 g, accompanied by activation of the TGF-β/Smad signaling pathways was detected in fibrotic liver tissues of mice and isolated HSCs with chronic liver injury induced by CCl_4 treatment. Overexpression of Gadd45 a reduced the expression of extracellular matrix proteins and α-SMA in HSCs, whereas transient knockdown of Gadd45 a with si RNA reversed this process. Gadd45 a inhibited the activity of a plasminogen activator inhibitor-1 promoter construct and(CAGA)_9 MLP-Luc, an artificial Smad3/4-specific reporter, as well as reduced the phosphorylation and nuclear translocation of Smad3. Gadd45 a showed protective effects by scavenging reactive oxygen species and upregulating antioxidant enzymes.CONCLUSION: Gadd45 a may counteract hepatic fibrosis by regulating the activation of HSCs via the inhibition of TGF-β/Smad signaling.展开更多
Functional dyspepsia(FD) is a common and frequently occurring disease in clinic. With the infuence of environmental factors, social factors and dietary factors, the incidence rate of FD in the general population is ye...Functional dyspepsia(FD) is a common and frequently occurring disease in clinic. With the infuence of environmental factors, social factors and dietary factors, the incidence rate of FD in the general population is yearly increasing. Traditional Chinese medicine has a long history and far-reaching infuence in the treatment of FD. It can prevent and treat FD in the form of multiple-components, targets and channels,with obvious effect and prominent advantages. This article starts with the common syndrome types of FD, and discusses the research progress of single Chinese medicine, effective ingredients and the mechanism of traditional Chinese medicines in treating FD, in order to provide a theoretical basis for the treatment of FD with traditional Chinese medicines.展开更多
O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) me...O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S 112 GlcNAcylation) plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress- inducing agents. OGT mediated H2B Sl12 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S 112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). Mechanistically, H2B Sl12 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci for- mation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR).展开更多
文摘BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a rare autoimmune disorder.The symptoms of anti-NMDAR encephalitis include behavioral problems,speech problems,psychosis,seizures,and memory deficits,among others.However,laryngospasm is rare.We present the case of a patient with anti-NMDAR antibodies and severe laryngospasms.CASE SUMMARY The patient was a 15-year-old female with normal psychomotor development.She was initially admitted to our neurological intensive care unit with seizures.She received anti-epilepsy treatment,and the seizures disappeared.However,2 wk later,she developed behavioral problems and speech impairment.Then,she developed severe laryngospasms,which were treated with intubation and a tracheotomy.Antibodies against the NMDAR were detected in the patient’s cerebrospinal fluid.Therefore,she was diagnosed with anti-NMDAR encephalitis.In addition,she received intravenously administered immunoglobulins,and methylprednisolone was administered.The patient’s symptoms gradually improved,and she was discharged from our hospital.Approximately 9 mo later,the patient could speak sentences,walk independently,and carry out activities of daily living independently.Through our case report,we highlighted laryngospasm as an uncommon presentation in patients with anti-NMDAR encephalitis.CONCLUSION Laryngospasm may be an uncommon clinical manifestation of anti-NMDAR encephalitis.
基金Supported by Medicine and Health Research Programs of Zhejiang Province,No.2013KYB252the Science Foundation of the Science and Technology Commission of Ruian City,No.201302012
文摘AIM: To investigate the role of Gadd45 a in hepatic fibrosis and the transforming growth factor(TGF)-β/Smad signaling pathway.METHODS: Wild-type male BALB/c mice were treated with CCl_4 to induce a model of chronic liver injury. Hepatic stellate cells(HSCs) were isolated from the liver of BALB/c mice and were treated with small interfering RNAs(si RNAs) targeting Gadd45 a or the pc DNA3.1-Gadd45 a recombinant plasmid. Cellular α-smooth muscle actin(α-SMA), β-actin, type Ⅰ collagen, phosphoSmad2, phospho-Smad3, Smad2, Smad3, and Smad4 were detected by Western blots. The m RNA levels of α-SMA, β-actin, and type Ⅰ collagen were determined by quantitative real-time(q RT)-PCR analyses. Reactive oxygen species production was monitored by flow cytometry using 2,7-dichlorodihydrofluorescein diacetate.Gadd45a, Gadd45 b, anti-Gadd45 g, type Ⅰ collagen, and SMA local expression in liver tissue were measured by histologic and immunohistochemical analyses. RESULTS: Significant downregulation of Gadd45 a, but not Gadd45 b or Gadd45 g, accompanied by activation of the TGF-β/Smad signaling pathways was detected in fibrotic liver tissues of mice and isolated HSCs with chronic liver injury induced by CCl_4 treatment. Overexpression of Gadd45 a reduced the expression of extracellular matrix proteins and α-SMA in HSCs, whereas transient knockdown of Gadd45 a with si RNA reversed this process. Gadd45 a inhibited the activity of a plasminogen activator inhibitor-1 promoter construct and(CAGA)_9 MLP-Luc, an artificial Smad3/4-specific reporter, as well as reduced the phosphorylation and nuclear translocation of Smad3. Gadd45 a showed protective effects by scavenging reactive oxygen species and upregulating antioxidant enzymes.CONCLUSION: Gadd45 a may counteract hepatic fibrosis by regulating the activation of HSCs via the inhibition of TGF-β/Smad signaling.
文摘Functional dyspepsia(FD) is a common and frequently occurring disease in clinic. With the infuence of environmental factors, social factors and dietary factors, the incidence rate of FD in the general population is yearly increasing. Traditional Chinese medicine has a long history and far-reaching infuence in the treatment of FD. It can prevent and treat FD in the form of multiple-components, targets and channels,with obvious effect and prominent advantages. This article starts with the common syndrome types of FD, and discusses the research progress of single Chinese medicine, effective ingredients and the mechanism of traditional Chinese medicines in treating FD, in order to provide a theoretical basis for the treatment of FD with traditional Chinese medicines.
基金supported by the grants from the National Program on Key Basic Research Project (Nos. 2013CB910300 and 2012CB910300 to H.P.)the International Science and Technology Cooperation Program of China (No. 2015DFA31680)+2 种基金the One Thousand Young Talent Program (to H.P.)the State Key Laboratory of Proteomics (No. SKLP-O201303 to C.Y.)the National Natural Science Foundation of China (No. 31371433 to H.P.)
文摘O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediated O-GlcNAcylation of histone H2B Ser 112 (H2B S 112 GlcNAcylation) plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress- inducing agents. OGT mediated H2B Sl12 GlcNAcylation increased locally upon the induction of double-strand breaks (DSBs), and depletion of OGT or overexpression of H2B S 112A mutant impaired homologous recombination (HR) and nonhomologous end-joining (NHEJ). Mechanistically, H2B Sl12 GlcNAcylation could bind Nijmegen breakage syndrome 1 (NBS1) and regulate NBS1 foci for- mation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response (DDR).