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Background and ObjectiveThe efficacy and safety of edaravone for the treatment of amyotrophic lateral sclerosis (ALS) remain unclear. The aim of this meta-analysis was to provide evidence-based medical guidance and advice for the ...
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Background and ObjectiveThe efficacy and safety of edaravone for the treatment of amyotrophic lateral sclerosis (ALS) remain unclear. The aim of this meta-analysis was to provide evidence-based medical guidance and advice for the clinical application of edaravone in the treatment of ALS. MethodsPubMed, Embase, Chinese Biomedical Literature Database (CBM), Cochrane Library and Web of Science were searched through 09 March 2022 for randomized controlled trials (RCTs) on the safety and efficacy of edaravone versus placebo during follow-up of patients with ALS. A summary of the outcome measures with GRADE was performed. This study was registered on PROSPERO (ID: CRD 42022319997). ResultsFive RCTs with a total of 566 participants were included, and there was a significant difference (mean difference [MD] 1.33, 95% confidence interval [CI] 0.33-2.34; p = 0.009) in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score between the treatment and placebo groups. The edaravone group had an increased grip strength (MD 0.26, 95% CI 0.03-0.49; p = 0.03) and modified Norris Scale score (MD 2.81, 95% CI 1.18-4.43; p = 0.0007). However, there were no significant differences between groups for the change in forced vital capacity (FVC)% (MD 0.55, 95% CI - 3.15 to 4.24; p = 0.77), pinch strength (MD 0.05, 95% CI - 0.05 to 0.16; p = 0.33) or Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) score (MD - 4.76, 95% CI - 9.56 to 0.03; p = 0.05). The incidence of adverse events (AEs) (risk ratio [RR] 0.09, 95% CI 0.93-1.05; p = 0.65), serious adverse events (SAEs) (RR 0.72, 95% CI 0.52-1.00; p = 0.05) and the number of deaths (risk difference [RD] 0.00, 95% CI - 0.02 to 0.03; p = 0.83) were not statistically different from the placebo group. The quality of evidence was low only for SAEs, and the remaining outcome measures were of moderate quality. ConclusionsCompared with placebo, edaravone may provide potential clinical benefits in the treatment of ALS and may not increase the number of AEs and deaths. However, due to the low-quality evidence of the included studies and the small sample size, more high-quality and high-standard research evidence is needed to confirm these results. Protocol RegistrationThis study was registered on PROSPERO (ID: CRD 42022319997).
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Populations of water starwort, a winter annual or biennial weed in the pink family (Caryophyllaceae), can no longer be controlled by tribenuron following successive use of this herbicide over several years. Whole-plant bioassays h...
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Populations of water starwort, a winter annual or biennial weed in the pink family (Caryophyllaceae), can no longer be controlled by tribenuron following successive use of this herbicide over several years. Whole-plant bioassays have established that the resistant water starwort populations JS17, JS08, JS16, and JS07 showed high-level (from 203-fold to 565-fold) resistance to tribenuron. In vitro acetolactate synthase (ALS) assays revealed that resistance was due to reduced sensitivity of the ALS enzyme to tribenuron. The half-maximal inhibitory concentration (I50) values for JS17, JS08, JS16, and JS07 were 72, 71, 70, and 76 times greater, respectively, than were those of the susceptible population JS24. This altered ALS sensitivity in the resistant populations was due to a mutation in the ALS gene resulting in a Pro197 to Ser substitution (JS17, JS08, and JS16) and a Pro197 to Leu substitution (JS07). This study established the first documented case, to our knowledge, of evolved tribenuron resistance in water starwort and concluded that the molecular basis of resistance is due, at least in part, to a target-site modification at Pro197 in the ALS gene.
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Water chickweed is a widespread and competitive winter annual or biennial weed of wheat in China. One Water chickweed population (HN02) resistant to several acetolactate synthase (ALS) inhibitors was found in Henan province of Chi...
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Water chickweed is a widespread and competitive winter annual or biennial weed of wheat in China. One Water chickweed population (HN02) resistant to several acetolactate synthase (ALS) inhibitors was found in Henan province of China. Whole-plant bioassays showed that HN02 was high resistance to tribenuron (292.05-flod). In vitro ALS assays revealed that resistance was due to reduced sensitivity of the ALS enzyme to tribenuron. The I50 value for HN02 was 85.53 times greater respectively than that of susceptible population (SD05). This altered ALS sensitivity in the resistant population was due to a mutation in the ALS gene resulting in a Pro197 to Ser substitution. Cross-resistance experiments indicated that HN02 exhibited various resistance patterns to pyrithiobac-sodium, florasulam and pyroxsulam, without resistance to imazethapyr. This is the first report of tribenuron-resistant Water chickweed in Henan province of China, target-site based resistance was established as being due to an insensitive form of ALS, resulting from a Pro to Ser substitution at amino acid position 197 in the ALS gene.
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Mutations in several genes have been associated with amyotrophic lateral sclerosis (ALS). Only a few genes seem to account for significant percentage of ALS cases (SOD1, TARDBP, C9OFR72, FUS, OPTN, and VCP), with many others causi...
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Mutations in several genes have been associated with amyotrophic lateral sclerosis (ALS). Only a few genes seem to account for significant percentage of ALS cases (SOD1, TARDBP, C9OFR72, FUS, OPTN, and VCP), with many others causing a few cases each.
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The identifi cation of genetic and epigenetic factors that are associated with an increased risk of developing amyotrophic lateral sclerosis (ALS), or that modify the age of onset or rate of progression, requires a multimodal rese...
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The identifi cation of genetic and epigenetic factors that are associated with an increased risk of developing amyotrophic lateral sclerosis (ALS), or that modify the age of onset or rate of progression, requires a multimodal research strategy, facilitated through international collaboration. The discovery of several ALS genes strongly linked to RNA biology, the proteasome pathway, and axonal transport suggest they have an important role in pathogenesis, but the immense complexity of these processes is also apparent. The increasing rate of genetic discoveries brings the hope of designing more targeted and effi cacious therapies.
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Our objective was to analyze gene expression pattern in muscles from patients with amyotrophic lateral sclerosis (ALS) and multifocal motor neuropathy (MMN) compared to controls. Biopsied skeletal muscles from three ALS, three MMN...
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Our objective was to analyze gene expression pattern in muscles from patients with amyotrophic lateral sclerosis (ALS) and multifocal motor neuropathy (MMN) compared to controls. Biopsied skeletal muscles from three ALS, three MMN and three control subjects had total RNA extracted and subjected to genome-wide gene expression analysis using Affymetrix GeneChip Exon 1.0 ST array. The most significant expression pattern differences were confirmed with RT-PCR in four additional ALS patients. Results showed that over 3000 genes were identified across the groups using q < 10%. Among 50 genes that were overexpressed only in the ALS group were: leucine-rich repeat kinase-2, follistatin, collagen type XIX alpha-1, ceramide kinase-like, sestrin-3 and CXorf64. No genes were significantly overexpressed in MMN alone. Underexpressed genes only in ALS included actinin α3, fructose-1,6-bisphosphatase-2 and homeobox C10; whereas only in MMN: hemoglobin A1 and CXorf64. Ankyrin repeat domain-1 was overexpressed in both groups. Underexpressed genes in both groups included myosin light chain kinase-2, enolase-3 and 6-phosphofructo-2-kinase/ fructose-2,6-biphosphatase-1. Validation analysis using RT-PCR confirmed the data for leucine-rich repeat kinase-2, follistatin, collagen type XIX alpha-1, ceramide kinase-like, sestrin-3 and CXorf64. In conclusion, there is differential tissue-specific gene expression in patients with ALS relative to MMN and controls. Further studies are necessary to evaluate the identified genes in larger patient groups and different tissues.
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Some FUS mutations have been observed in patients with the juvenile form of Amyotrophic Lateral Sclerosis starting before 25. years. We report an 11-year-old girl affected by sporadic juvenile ALS with a rapid course resulting in ...
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Some FUS mutations have been observed in patients with the juvenile form of Amyotrophic Lateral Sclerosis starting before 25. years. We report an 11-year-old girl affected by sporadic juvenile ALS with a rapid course resulting in tracheostomy after 14. months from the onset. Sequencing FUS gene revealed a de novo P525L mutation. Our findings, together with literature data, indicate that this mutation is consistently associated with a specific phenotype characterized by juvenile onset, severe course and high proportion of de novo mutations in sporadic cases.
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The rapid evolution and spread of glyphosate-resistant (GR) kochia in the Northern Great Plains is an increasing threat to GR cropping systems and conservation tillage practices common in this region. GR kochia accessions with 4.6...
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The rapid evolution and spread of glyphosate-resistant (GR) kochia in the Northern Great Plains is an increasing threat to GR cropping systems and conservation tillage practices common in this region. GR kochia accessions with 4.6-to 11-fold levels of resistance to glyphosate have recently been reported in Montana. Those GR kochia accessions were also suspected to be resistant to acetolactate synthase (ALS) inhibitors, i.e., multiple herbicide-resistant (MHR) kochia. In this research, the level of resistance to the ALS-inhibitor herbicides (sulfonylureas) and the molecular mechanisms conferring resistance to glyphosate and ALS-inhibitor herbicides in MHR kochia was investigated. On the basis of whole-plant dose-response assays, MHR kochia accessions (GIL01, JOP01, and CHES01) were 9.3- to 30-fold more resistant to premixed thifensulfuron methyl + tribenuron methyl + metsulfuron methyl than the susceptible (SUS) accession. In an in vivo leaf-disk shikimate assay, MHR plants accumulated less shikimate than the SUS plants at a discriminate dose of 100 mu M glyphosate. Sequencing of the conserved region of EPSPS revealed no target-site mutation at Thr(102) or Pro(106) residue. MHR kochia accessions had increased relative EPSPS gene copies (similar to 4 to 10) compared with the SUS accession (single copy). Furthermore, MHR kochia accumulated higher EPSPS protein compared with the SUS plants. Resistance to the ALS-inhibitor herbicides was conferred by Pro(197) amino acid substitution (proline to glutamine). EPSPS gene amplification and a single target-site mutation at Pro(197) in ALS gene confer resistance to glyphosate and ALS-inhibitor herbicides, respectively, in MHR kochia accessions from Montana. This is the first confirmation of occurrence of MHR kochia in Montana.
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Abstract Complaints of control failures with acetolactate synthase (ALS)- and protoporphyrinogen oxidase (PPO)-inhibiting herbicides on redroot pigweed (Amaranthus retroflexus L.) were reported in conventional soybean [Glycine max...
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Abstract Complaints of control failures with acetolactate synthase (ALS)- and protoporphyrinogen oxidase (PPO)-inhibiting herbicides on redroot pigweed (Amaranthus retroflexus L.) were reported in conventional soybean [Glycine max (L.) Merr.] fields in North Carolina. Greenhouse dose–response assays confirmed that the Camden County and Pasquotank County populations were less sensitive to ALS- and PPO-inhibiting herbicides compared with susceptible A. retroflexus populations, suggesting the evolution of resistance to these herbicides. Sanger sequencing of target genes determined the Camden County population carried a Trp-574-Leu mutation in the ALS gene and an Arg-98-Gly mutation in the PPX2 gene, while the Pasquotank County population carried a His-197-Pro mutation in the ALS gene (first documentation of the mutation in the Amaranthus genus), but no mutation was detected in the PPX2 gene. Single-nucleotide polymorphism (SNP) genotyping assays were developed to enable efficient screening of future control failures in order to limit the spread of these herbicide-resistant populations. In addition, preliminary testing of these assays revealed the three mutations were ubiquitous in the respective populations. These two populations represent the first confirmed cases of PPO-inhibiting herbicide-resistant A. retroflexus in the United States, as well as the first confirmed cases of this particular herbicide-resistance profile in A. retroflexus inhabiting North America. While no mutation was found in the PPX2 gene of the Pasquotank County population, we suggest that this population has evolved resistance to PPO-inhibiting herbicides, but the mechanism of resistance is to be determined.
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Aluminum (Al) induced genes were isolated from a wild plant, Andropogon virginicus L. by a method involving arbitrarily primed PCR-based RNA finger printing. One of the clones, AP18-2-1, was induced in both roots and shoots by Al ...
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Aluminum (Al) induced genes were isolated from a wild plant, Andropogon virginicus L. by a method involving arbitrarily primed PCR-based RNA finger printing. One of the clones, AP18-2-1, was induced in both roots and shoots by Al and diamide treatments, and slightly by Cu and Zn treatments. Full-length cDNA (2287 bp) was obtained by RACE (rapid amplification of cDNA ends) PCR and DNA sequencing indicated that it encoded a half-type ABC transporter that was highly homologous to other ABCG family genes. The Al-induced transporter gene derived from A. virginicus L. was therefore designated AvABCG1. The AvABCG1 gene conferred tolerance to Al, Cu and diamide in Arabidopsis thaliana transformants. A fusion protein (AvABCG1::GFP) was localized in the cell membrane region. Immunohistological analysis of the native protein in A. virginicus L indicated that it localized to both exodermis and endodermis in roots, and to the vascular bundle sheath and its extensions in both upper and lower epidermal cells in leaves. Fluorescent measurement showed that absorbed Al was detected in almost the same areas as the AvABCG1 protein in both root and leaf. We conclude that the AvABCG1 transporter may confer Al tolerance by accumulating absorbed Al ions in specific regions of the plant. (C) 2015 Elsevier B.V. All rights reserved.
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