Amorpha-4,11-diene synthase (ADS) and Cyt P450 monooxygenase (CYP71AV1) in Artemisia annua L. are two key enzymes involved in the biosynthesis of artemisinin. The promoters of ADS and CYP71AV1 contain E-box elements, which are putative binding sites for basic helix-loop-helix (bHLH) transcription factors. This study successfully isolated a bHLH transcription factor gene from A. annua, designated as AabHLH1, from a cDNA library of the glandular secretory trichomes (GSTs) in which artemisinin is synthesized and sequestered. AabHLH1 encodes a protein of 650 amino acids containing one putative bHLH domain. AabHLH1 and ADS genes were strongly induced by ABA and the fungal elicitor, chitosan. The transient expression analysis of the AabHLH1-green fluorescent protein (GFP) reporter gene revealed that AabHLH1 was targeted to nuclei. Biochemical analysis demonstrated that the AabHLH1 protein was capable of binding to the E-box cis-elements, present in both ADS and CYP71AV1 promoters, and possessed transactivation activity in yeast. In addition, transient co-transformation of AabHLH1 and CYP71AV1Pro::GUS in A. annua leaves showed a significant activation of the expression of the GUS (β-glucuronidase) gene in transformed A. annua, but mutation of the E-boxes resulted in abolition of activation, suggesting that the E-box is important for the CYP71AV1 promoter activity. Furthermore, transient expression of AabHLH1 in A. annua leaves increased transcript levels of the genes involved in artemisinin biosynthesis, such as ADS, CYP71AV1 and HMGR. These results suggest that AabHLH1 can positively regulate the biosynthesis of artemisinin.
BackgroundGastric cancer is a major health problem, and frailty and sarcopenia will affect the postoperative outcomes in older people. However, there is still no systematic review to determine the role of frailty and sarcopenia in predicting postoperative outcomes among older patients with gastric cancer who undergo gastrectomy surgery.MethodsWe searched Embase, Medline through the Ovid interface and PubMed websites to identify potential studies. All the search strategies were run on August 24, 2016. We searched the Google website for unpublished studies on June 1, 2017. The data related to the endpoints of gastrectomy surgery were extracted. Odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the association between sarcopenia and adverse postoperative outcomes by using Stata version 11.0. PRISMA guidelines for systematic reviews were followed.ResultsAfter screening 500 records, we identified eight studies, including three prospective cohort studies and five retrospective cohort studies. Only one study described frailty, and the remaining seven studies described sarcopenia. Frailty was statistically significant for predicting hospital mortality (OR 3.96; 95% CI: 1.12–14.09, P = 0.03). Sarcopenia was also associated with postoperative outcomes (pooled OR 3.12; 95% CI: 2.23–4.37). No significant heterogeneity was observed across these pooled studies (Chi2 = 3.10, I2 = 0%, P = 0.685).ConclusionSarcopenia and frailty seem to have significant adverse impacts on the occurrence of postoperative outcomes. Well-designed prospective cohort studies focusing on frailty and quality of life with a sufficient sample are needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12877-017-0569-2) contains supplementary material, which is available to authorized users.
Background Sarcopenia is a serious public health concern among older adults worldwide. Exercise is the most common intervention for sarcopenia. This study aimed to compare the effectiveness of different exercise types for older adults with sarcopenia. Methods Randomized controlled trials (RCTs) that examined the effectiveness of exercise interventions on patient-important outcomes for older adults with sarcopenia were eligible. We systematically searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials via Ovid until 3 June 2022. We used frequentist random-effects network meta-analyses to summarize the evidence and applied the Grading of Recommendations, Assessment, Development, and Evaluations framework to rate the certainty of evidence. Results Our search identified 5988 citations, of which 42 RCTs proved eligible with 3728 participants with sarcopenia (median age: 72.9 years, female: 73.3%) with a median follow-up of 12 weeks. We are interested in patient-important outcomes that include mortality, quality of life, muscle strength and physical function measures. High or moderate certainty evidence suggested that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life compared to usual care (standardized mean difference from 0.68 to 1.11). Moderate certainty evidence showed that resistance and balance exercise plus nutrition (mean difference [MD]: 4.19 kg) was the most effective for improving handgrip strength (minimally important difference [MID]: 5 kg). Resistance and balance exercise with or without nutrition (MD: 0.16 m/s, moderate) were the most effective for improving physical function measured by usual gait speed (MID: 0.1 m/s). Moderate certainty evidence showed that resistance and balance exercise (MD: 1.85 s) was intermediately effective for improving physical function measured by timed up and go test (MID: 2.1 s). High certainty evidence showed that resistance and aerobic, or resistance and balance, or resistance and aerobic exercise plus nutrition (MD from 1.72 to 2.28 s) were intermediately effective for improving physical function measured by the five-repetition chair stand test (MID: 2.3 s). Conclusions In older adults with sarcopenia, high or moderate certainty evidence showed that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life. Adding nutritional interventions to exercise had a larger effect on handgrip strength than exercise alone while showing a similar effect on other physical function measures.
Objectives To assess the role of a pre-chemotherapy frailty index based on routine laboratory data in predicting mortality and chemotherapy adverse reactions among older patients with primary lung cancer. Design Retrospective cohort study Setting West China Hospital, Chengdu, China Participants We included patients aged ≥60 years with primary lung cancer receiving the first course of chemotherapy. Measurements Data were collected from medical records, local government death databases or telephone interviews. Outcomes included chemotherapy adverse reactions and all-cause mortality. We constructed a frailty index based on 44 laboratory variables (FI-LAB) before chemotherapy, and chose the following cutoff points: robust (0.0–0.2), pre-frail (0.2–0.35) and frail (≥0.35). Results We included 1,020 patients (71.4% male; median age: 65 years old). Both pre-frailty and frailty was associated with any chemotherapy adverse reactions and infections during chemotherapy (OR=3.48, 95%CI: 1.77–6.87; OR=3.58, 95%CI: 1.55–8.26, respectively). Frail patients had a shorter median overall survival rate compared to robust patients (18.05 months vs 38.89 months, log-rank p <0.001). After adjusting for some potential confounding variables, the risk of all-cause mortality was dramatically increased in frail patients (HR:2.13, 95% CI:1.51–3.00) with an average follow-up of 3.9 years. Each 0.01 or per standard deviation (SD) increase in the FI-LAB value significantly increased the HR of death by 2.0% (HR:1.02, 95% CI: 1.01–1.03) and 23.0% (HR: 1.23, 95% CI: 1.13–1.34), respectively. Conclusions Frailty assessed by routine laboratory data indicates increased risks of chemotherapy adverse reactions and death in older patients with primary lung cancer receiving the first course of chemotherapy.
BackgroundThe aim of this study was to assess the disk diffusion technique against E‐test as a routine antibiotic susceptibility testing method for Helicobacter pylori.Materials and methodsSusceptibilities of 301 H pylori clinical isolates were simultaneously profiled by E‐test and disk diffusion method for levofloxacin (5‐μg disk), clarithromycin (15‐μg disk), metronidazole (5‐μg disk), amoxicillin (10‐μg disk), and tetracycline (30‐μg disk). Furazolidone susceptibility was evaluated using a 100‐μg disk only. The correlation between MICs by E‐test and inhibition zone diameters by disk diffusion was assessed by linear regression analysis.ResultsCorrelation between inhibition zone diameters and MICs was found for levofloxacin (r = −.932), clarithromycin (r = −.894), and to a minor extent metronidazole (r = −.820). Using the linear regression analysis, the inhibition zone diameter breakpoints were calculated to be 29 mm for levofloxacin, 41 mm for clarithromycin, and 15 mm for metronidazole corresponding to the EUCAST‐recommended MIC breakpoints. The susceptibility agreement between E‐test and disk diffusion for levofloxacin, clarithromycin, and metronidazole was 98.6%, 96.0%, and 96.7%, respectively. The inhibition zone diameters recorded for the amoxicillin, tetracycline, and furazolidone were large (approximately 60 mm in mean), and a poor correlation was found between inhibition zone diameters and MICs for amoxicillin (r = −.594) and tetracycline (r = −.490).ConclusionsThe disk diffusion can be used as a routine H pylori susceptibility testing method for levofloxacin, clarithromycin, and metronidazole in clinical practice under the described technical conditions. The use of disk diffusion for amoxicillin, tetracycline, and furazolidone susceptibility testing needs to be further studied.
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