Oligodendrocyte-lineage cells, including NG2 glia, undergo prominent changes in various neurodegenerative disorders. Here, we identify a neuroprotective role for NG2 glia against prion toxicity. NG2 glia were activated after prion infection in cerebellar organotypic cultured slices (COCS) and in brains of prion-inoculated mice. In both model systems, depletion of NG2 glia exacerbated prion-induced neurodegeneration and accelerated prion pathology. Loss of NG2 glia enhanced the biosynthesis of prostaglandin E2 (PGE2) by microglia, which augmented prion neurotoxicity through binding to the EP4 receptor. Pharmacological or genetic inhibition of PGE2 biosynthesis attenuated prion-induced neurodegeneration in COCS and mice, reduced the enhanced neurodegeneration in NG2-glia-depleted COCS after prion infection, and dampened the acceleration of prion disease in NG2-glia-depleted mice. These data unveil a non-cell-autonomous interaction between NG2 glia and microglia in prion disease and suggest that PGE2 signaling may represent an actionable target against prion diseases.
To investigate the phenotype and genotype defect characteristics of a Chinese patient with hereditary factor XI deficiency.The activated partial thromboplastin time (APTT), prothrombin time (PT), FXI activity (FXI:C) of the proband and his relatives were measured by a clotting method using automatic coagulation analyzer. FXI antigen (FXI:Ag) was assayed by enzyme-linked immunosorbent assay (ELISA). Fifteen exons of the F11 gene were amplified by PCR and sequenced. Pymol software was used to analyze the novel mutations.The APTT of the proband was significantly prolonged (70.3 s, reference 34.5 s) with decreased FXI activity (6%, reference 50%-150%) and FXI antigen (1.9%, reference 50%-150%). The FXI activity and FXI antigen of his son was 31% and 39%, respectively. Two heterozygous F11 mutations were identified in the proband, which included a G to T substitution at nucleotide 1296 in exon 11 resulting in substitution of glycine by valine at codon 400 (p.Gly400Val) and a A to T substitution at nucleotide 1691 in exon 14 resulting in substitution of arginine (AGA) by a termination codon (TGA) at codon 532 (p.Arg532Ter). Analysis using Pymol indicated that the number of hydrogen bonds has changed, which led to a transformation of the structure of the FXI protein. The son of the proband was found to be heterozygous for the c.1296G to T (p.Gly400Val) mutation. NM_13142 c.1691A to T (p.Arg532Ter) is a novel mutation based on HGMD professional 2016.4. Based on 2015 Guidelines of ACMG, it is PVS1 (very strong pathogenicity).The compound heterozygous mutations of F11 NM_13142 c.1296G to T (p.Gly400Val) and F11 NM_13142 c.1691A to T(p.Arg532Ter) probably underlies the FXI deficiency in the proband.
AMA Guo D, Yang D, Zhang B, et al. The safety of Pfannenstiel incision for specimen extraction in laparoscopic colorectal surgery for colorectal cancer: a systematic review and meta-analysis. Videosurgery and Other Miniinvasive Techniques/Wideochirurgia i inne techniki małoinwazyjne. 2023. doi:10.5114/wiitm.2023.134194. APA Guo, D., Yang, D., Zhang, B., Xu, X., Yang, Z., & Zhao, Y. et al. (2023). The safety of Pfannenstiel incision for specimen extraction in laparoscopic colorectal surgery for colorectal cancer: a systematic review and meta-analysis. Videosurgery and Other Miniinvasive Techniques/Wideochirurgia i inne techniki małoinwazyjne. https://doi.org/10.5114/wiitm.2023.134194 Chicago Guo, DJingjing, Dong Yang, Bao Zhang, Xing Xu, Zhuo Yang, Yan Zhao, and Zhichao Zheng et al. 2023. "The safety of Pfannenstiel incision for specimen extraction in laparoscopic colorectal surgery for colorectal cancer: a systematic review and meta-analysis". Videosurgery and Other Miniinvasive Techniques/Wideochirurgia i inne techniki małoinwazyjne. doi:10.5114/wiitm.2023.134194. Harvard Guo, D., Yang, D., Zhang, B., Xu, X., Yang, Z., Zhao, Y., Zheng, Z., Meng, X., and Zhang, T. (2023). The safety of Pfannenstiel incision for specimen extraction in laparoscopic colorectal surgery for colorectal cancer: a systematic review and meta-analysis. Videosurgery and Other Miniinvasive Techniques/Wideochirurgia i inne techniki małoinwazyjne. https://doi.org/10.5114/wiitm.2023.134194 MLA Guo, DJingjing et al. "The safety of Pfannenstiel incision for specimen extraction in laparoscopic colorectal surgery for colorectal cancer: a systematic review and meta-analysis." Videosurgery and Other Miniinvasive Techniques/Wideochirurgia i inne techniki małoinwazyjne, 2023. doi:10.5114/wiitm.2023.134194. Vancouver Guo D, Yang D, Zhang B, Xu X, Yang Z, Zhao Y et al. The safety of Pfannenstiel incision for specimen extraction in laparoscopic colorectal surgery for colorectal cancer: a systematic review and meta-analysis. Videosurgery and Other Miniinvasive Techniques/Wideochirurgia i inne techniki małoinwazyjne. 2023. doi:10.5114/wiitm.2023.134194.
Although prion infections cause cognitive impairment and neuronal death, transcriptional and translational profiling shows progressive derangement within glia but surprisingly little changes within neurons. Here we expressed PrP C selectively in neurons, astrocytes or oligodendrocytes of mice. After prion infection, both astrocyte and neuron-restricted PrP C expression led to copious brain accumulation of PrP Sc . As expected, neuron-restricted expression was associated with typical prion disease. However, mice with astrocyte-restricted PrP C expression experienced a normal life span, did not develop clinical disease, and did not show astro- or microgliosis. Besides confirming that PrP Sc is innocuous to PrP C -deficient neurons, these results show that astrocyte-born PrP Sc does not activate the extreme neuroinflammation that accompanies the onset of prion disease and precedes any molecular changes of neurons. This points to a nonautonomous mechanism by which prion-infected neurons instruct astrocytes and microglia to acquire a specific cellular state that, in turn, drives neural dysfunction.
Objective. To compare features of SS in RA with primary SS and RA without SS. Methods. Patients hospitalized between January 2007 and December 2010 were retrospectively studied. Seventy-four cases of overlap RA and SS (RA/SS) among 509 cases of RA were identified. Cases of SS (n = 187) detected during the same period acted as controls. Results. Among those with RA/SS, there were 46 cases of RA-onset SS and 12 cases of SS-onset RA. Sixteen patients had simultaneous-onset RA and SS. Compared with RA without SS, RA/SS patients had more severe arthritis; a higher incidence of haematological abnormality, fever and rash; and a higher frequency of RF, ANAs and anti-SSA and anti-SSB antibodies (P < 0.05). Compared with primary SS, RA/SS patients were older, had more severe arthritis, anaemia and lung involvement; a lower incidence of fever, rash, leucopenia, thrombocytopenia and hyperthyroidism; and a higher frequency of RF, anti-keratin antibody, anti-perinuclear factor and anti-cyclic citrullinated antibodies (P < 0.05). Compared with RA and primary SS, RA/SS patients had higher disease activity scores of both RA and SS. Conclusion. RA/SS patients have distinctive features, with more complications and systemic involvement. In addition, disease activity is higher in RA/SS.
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