Author Report for: Shi RNo contact information in database for Shi R
Guo Y, He Z, Chen Z, Chen F, Wang C, Zhou W, Liu J, Liu H, Shi R Ref: Theranostics, 13:1826, 2023 : PubMed ESTHER: Guo_2023_Theranostics_13_1826 PubMedSearch: Guo 2023 Theranostics 13 1826 PubMedID: 37064881 Abstract Rationale: Pulmonary hypertension (PH) secondary to lung fibrosis belongs to WHO Group III, one of the most common subgroups of PH; however, it lacks effective treatment options. Cholinesterase inhibitor donepezil (DON) has been shown to effectively improve Group I PH. However, its effects on Group III PH are unknown. Methods: A lung fibrosis-induced PH mouse model was constructed using a single intratracheal instillation of bleomycin (BLM), after which DON was administered daily. Pulmonary artery and right ventricle (RV) remodeling were evaluated at the end of the study. Lung tissue in each group was analyzed using RNA sequencing, and the results were further verified with datasets from patients with PH. The mechanisms underlying DON-induced effects on PH were verified both in vivo and in vitro. Results: DON effectively improved pulmonary artery and RV remodeling in the BLM-induced mouse model. Transcriptomic profiles of lung tissue indicated that the expression of inflammatory and fibrotic genes was significantly changed in this process. In the animal model and patients with PH, T helper 17 lymphocytes (Th17) were the most common inflammatory cells infiltrating the lung tissue. DON significantly inhibited lung fibroblast activation; thus, preventing lung fibrosis and reducing the inflammatory response and Th17 cell infiltration in the BLM-induced lung tissue. In addition, Th17 cells could activate lung fibroblasts by secreting IL17A, and DON-mediated inhibition of Th17 cell differentiation was found to depend on the alpha7nAchR-JAK2-STAT3 pathway. Conclusion: DON can alleviate lung fibrosis and PH in an experimental mouse model. It inhibited pro-inflammatory Th17 cell differentiation, which is dependent on a cholinergic receptor pathway, thereby regulating fibroblast activation. Title: Neuropathy target esterase activity predicts retinopathy among PNPLA6 disorders Liu J, He Y, Lwin C, Han M, Guan B, Naik A, Bender C, Moore N, Huryn LA and Hufnagel RB <35 more author(s)> Liu J, He Y, Lwin C, Han M, Guan B, Naik A, Bender C, Moore N, Huryn LA, Sergeev Y, Qian H, Zeng Y, Dong L, Liu P, Lei J, Haugen CJ, Prasov L, Shi R, Dollfus H, Aristodemou P, Laich Y, Nemeth AH, Taylor J, Downes S, Krawczynski M, Meunier I, Strassberg M, Tenney J, Gao J, Shear MA, Moore AT, Duncan JL, Menendez B, Hull S, Vincent A, Siskind CE, Traboulsi EI, Blackstone C, Sisk R, Utz V, Webster AR, Michaelides M, Arno G, Synofzik M, Hufnagel RB (- 35) Ref: Biorxiv, :, 2023 : PubMed ESTHER: Liu_2023_bioRxiv__ PubMedSearch: Liu 2023 bioRxiv PubMedID: 37333224 Abstract Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism, and hair anomalies. PNPLA6 encodes Neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a clinical meta-analysis of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6 -associated clinical diagnoses unambiguously reclassified 10 variants as likely pathogenic and 36 variants as pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship and the generation of a preclinical animal model pave the way for therapeutic trials, using NTE as a biomarker. Title: Structural insights into the putative bacterial acetylcholinesterase ChoE and its substrate inhibition mechanism Pham VD, To TA, Gagne-Thivierge C, Couture M, Lague P, Yao D, Picard ME, Lortie LA, Attere SA and Shi R <3 more author(s)> Pham VD, To TA, Gagne-Thivierge C, Couture M, Lague P, Yao D, Picard ME, Lortie LA, Attere SA, Zhu X, Levesque RC, Charette SJ, Shi R (- 3) Ref: Journal of Biological Chemistry, :, 2020 : PubMed ESTHER: Pham_2020_J.Biol.Chem__ PubMedSearch: Pham 2020 J.Biol.Chem PubMedID: 32371400 Abstract Mammalian acetylcholinesterase (AChE) is well studied, being important in both cholinergic brain synapses and the peripheral nervous systems and also a key drug target for many diseases. In contrast, little is known about the structures and molecular mechanism of prokaryotic acetylcholinesterases. We report here the structural and biochemical characterization of ChoE, a putative bacterial acetylcholinesterase from Pseudomonas aeruginosa. Analysis of wild-type (WT) and mutant strains indicated that ChoE is indispensable for P. aeruginosa growth with acetylcholine as the sole carbon and nitrogen source. The crystal structure of ChoE at 1.35 A resolution revealed that this enzyme adopts a typical fold of the SGNH hydrolase family. Although ChoE and eukaryotic AChEs catalyze the same reaction, their overall structures bear no similarities constituting an interesting example of convergent evolution. Among Ser-38, Asp-285, and His-288 of the catalytic triad residues, only Asp-285 was not essential for ChoE activity. Combined with kinetic analyses of WT and mutant proteins, multiple crystal structures of ChoE complexed with substrates, products, or reaction intermediate revealed the structural determinants for substrate recognition, snapshots of the various catalytic steps, and the molecular basis of substrate inhibition at high substrate concentrations. Our results indicate that substrate inhibition in ChoE is due to acetate release being blocked by the binding of a substrate molecule in a nonproductive mode. Owing to the distinct overall folds and significant differences of the active site between ChoE and eukaryotic AChEs, these structures will serve as a prototype for other prokaryotic acetylcholinesterases. Title: Glycogen synthase kinase-3beta suppresses the expression of protein phosphatase methylesterase-1 through beta-catenin Jin N, Shi R, Jiang Y, Chu D, Gong CX, Iqbal K, Liu F Ref: Aging (Albany NY), 11:9672, 2019 : PubMed ESTHER: Jin_2019_Aging.(Albany.NY)_11_9672 PubMedSearch: Jin 2019 Aging.(Albany.NY) 11 9672 PubMedID: 31714894 Gene_locus related to this paper: human-PPME1 Abstract Protein phosphatase 2A (PP2A) is the major tau phosphatase. Its activity toward tau is regulated by the methylation of PP2A catalytic subunit (PP2Ac) at Leu309. Protein phosphatase methylesterase-1 (PME-1) demethylates PP2Ac and suppresses its activity. We previously found that glycogen synthase kinase-3beta (GSK-3beta) suppresses PME-1 expression. However, the underlying molecular mechanism is unknown. In the present study, we analyzed the promoter of PME-1 gene and found that human PME-1 promoter contains two lymphoid enhancer binding factor-1/T-cell factor (LEF1/TCF) cis-elements in which beta-catenin serves as a co-activator. beta-catenin acted on these two cis-elements and promoted PME-1 expression. GSK-3beta phosphorylated beta-catenin and suppressed its function in promoting PME-1 expression. Inhibition and activation of GSK-3beta by PI3K-AKT pathway promoted and suppressed, respectively, PME-1 expression in primary cultured neurons, SH-SY5Y cells and in the mouse brain. These findings suggest that GSK-3beta phosphorylates beta-catenin and suppresses its function on PME-1 expression, resulting in an increase of PP2Ac methylation. Title: Macrophage ABHD5 Suppresses NFkappaB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis Shang S, Ji X, Zhang L, Chen J, Li C, Shi R, Xiang W, Kang X, Zhang D and Miao H <6 more author(s)> Shang S, Ji X, Zhang L, Chen J, Li C, Shi R, Xiang W, Kang X, Zhang D, Yang F, Dai R, Chen P, Chen S, Chen Y, Li Y, Miao H (- 6) Ref: Cancer Research, 79:5513, 2019 : PubMed ESTHER: Shang_2019_Cancer.Res_79_5513 PubMedSearch: Shang 2019 Cancer.Res 79 5513 PubMedID: 31439546 Gene_locus related to this paper: human-ABHD5 Abstract Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFkappaB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFkappaB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5513/F1.large.jpg. Title: Astragalus Polysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity in Caenorhabditis elegans Li H, Shi R, Ding F, Wang H, Han W, Ma F, Hu M, Ma CW, Huang Z Ref: Oxid Med Cell Longev, 2016:4856761, 2016 : PubMed ESTHER: Li_2016_Oxid.Med.Cell.Longev_2016_4856761 PubMedSearch: Li 2016 Oxid.Med.Cell.Longev 2016 4856761 PubMedID: 27885333 Abstract Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson's disease (PD). However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic gene egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential of Astragalus polysaccharide in neurodegeneration. Title: Species variation in small molecule components of animal vitreous Mains J, Tan LE, Zhang T, Young L, Shi R, Wilson C Ref: Invest Ophthalmol Vis Sci, 53:4778, 2012 : PubMed ESTHER: Mains_2012_Invest.Ophthalmol.Vis.Sci_53_4778 PubMedSearch: Mains 2012 Invest.Ophthalmol.Vis.Sci 53 4778 PubMedID: 22669713 Abstract PURPOSE: We characterized differences in biochemical composition of the vitreous of different animal species with respect to small molecule constituents. METHODS: Vitreous samples were extracted from sheep, pig, Dutch Belted rabbits, and New Zealand white rabbits. The vitreous samples were investigated for acetylcholinesterase (AChE) activity and, in addition, were subjected to metabolomics determination using mass spectrometry. RESULTS: AChE activity varied across the species investigated with greater activity noted in larger animals. Principal component analysis demonstrated species differentiation in relation to metabolomic profile. Key peaks identified the importance of animal diet on small molecule composition of the vitreous. CONCLUSIONS: Our results highlighted principal and consistent differences in small molecule composition and enzymatic activity of the vitreous depending on species. Interesting differences were demonstrated, showing that diet potentially can impact on components of and metabolites contained within the vitreous. Material will be exchanged between vascular and retinal tissue with the vitreous compartment and as a nonvascular, slowly equilibrating "sink" might reflect changes in transporter activity. As a first step, understanding the differences in the metabolic profile of vitreous from different species may impact interpretation of such activity across different species. Title: The Medicago genome provides insight into the evolution of rhizobial symbioses Young ND, Debelle F, Oldroyd GE, Geurts R, Cannon SB, Udvardi MK, Benedito VA, Mayer KF, Gouzy J and Roe BA <114 more author(s)> Young ND, Debelle F, Oldroyd GE, Geurts R, Cannon SB, Udvardi MK, Benedito VA, Mayer KF, Gouzy J, Schoof H, Van de Peer Y, Proost S, Cook DR, Meyers BC, Spannagl M, Cheung F, De Mita S, Krishnakumar V, Gundlach H, Zhou S, Mudge J, Bharti AK, Murray JD, Naoumkina MA, Rosen B, Silverstein KA, Tang H, Rombauts S, Zhao PX, Zhou P, Barbe V, Bardou P, Bechner M, Bellec A, Berger A, Berges H, Bidwell S, Bisseling T, Choisne N, Couloux A, Denny R, Deshpande S, Dai X, Doyle JJ, Dudez AM, Farmer AD, Fouteau S, Franken C, Gibelin C, Gish J, Goldstein S, Gonzalez AJ, Green PJ, Hallab A, Hartog M, Hua A, Humphray SJ, Jeong DH, Jing Y, Jocker A, Kenton SM, Kim DJ, Klee K, Lai H, Lang C, Lin S, Macmil SL, Magdelenat G, Matthews L, McCorrison J, Monaghan EL, Mun JH, Najar FZ, Nicholson C, Noirot C, O'Bleness M, Paule CR, Poulain J, Prion F, Qin B, Qu C, Retzel EF, Riddle C, Sallet E, Samain S, Samson N, Sanders I, Saurat O, Scarpelli C, Schiex T, Segurens B, Severin AJ, Sherrier DJ, Shi R, Sims S, Singer SR, Sinharoy S, Sterck L, Viollet A, Wang BB, Wang K, Wang M, Wang X, Warfsmann J, Weissenbach J, White DD, White JD, Wiley GB, Wincker P, Xing Y, Yang L, Yao Z, Ying F, Zhai J, Zhou L, Zuber A, Denarie J, Dixon RA, May GD, Schwartz DC, Rogers J, Quetier F, Town CD, Roe BA (- 114) Ref: Nature, 480:520, 2011 : PubMed ESTHER: Young_2011_Nature_480_520 PubMedSearch: Young 2011 Nature 480 520 PubMedID: 22089132 Gene_locus related to this paper: medtr-b7fki4, medtr-b7fmi1, medtr-g7itl1, medtr-g7iu67, medtr-g7izm0, medtr-g7j641, medtr-g7jtf8, medtr-g7jtg2, medtr-g7jtg4, medtr-g7kem3, medtr-g7kml3, medtr-g7ksx5, medtr-g7leb3, medtr-q1s5d8, medtr-q1s9m3, medtr-q1t171, medtr-g7k9e1, medtr-g7k9e3, medtr-g7k9e5, medtr-g7k9e8, medtr-g7k9e9, medtr-g7lbp2, medtr-g7lch3, medtr-g7ib94, medtr-g7ljk8, medtr-g7i6w5, medtr-g7kvg4, medtr-g7iam1, medtr-g7iam3, medtr-g7l754, medtr-g7jr41, medtr-g7l4f5, medtr-g7l755, medtr-a0a072vyl4, medtr-g7jwk8, medtr-a0a072vhg0, medtr-a0a072vrv9, medtr-g7kmk5, medtr-a0a072uuf6, medtr-a0a072urp3, medtr-g7zzc3, medtr-g7ie19, medtr-g7kst7, medtr-a0a072u5k5, medtr-a0a072v056, medtr-scp1, medtr-g7kyn0, medtr-g7inw6, medtr-g7j3q3 Abstract Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing approximately 94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox. | |||||||
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