RESUMO
The plant Goniothalamus leiocarpus of the Annonaceae family is used as an alternative medicine in tropical regions. Applying high-speed counter current chromatography (HSCCC), eight new bioactive styrylpyrone isomers, including 6R,7S,8R,2'S-goniolactone B (1), 6S,7S,8S,2'S-goniolactone B (2), 6R,7R,8R,2'S-goniolactone B (3), 6R,7S,8S,2'S-goniolactone C (4), 6R,7S,8R,2'S-goniolactone C (5), 6S,7R,8S,2'S-goniolactone C (6), and two positional isomers, 6R,7R,8R,2'S-goniolactone G (7) and 6S,7R,8R,2'S-goniolactone G (8), were isolated from a chloroform fraction (2.1 g) of G. leiocarpus, which had a prominent spot by TLC analysis. The structures of the new compounds were elucidated by MS, NMR, IR, and UV spectra, and their absolute configurations were determined by Mosher's method, ECD, and X-ray diffraction analysis. The isolates are characteristic components found in plants of the genus Goniothalamus and consist of two structural moieties: a styrylpyrone and a dihydroflavone unit. The isolation of the eight new compounds demonstrates the effectiveness of HSCCC in separating the isomers of natural styrylpyrone. In a bioactivity assessment, compounds 1 and 6 exhibited cytotoxic effects against the human colon carcinoma cell lines LS513 and SW620 with IC50 values ranging from 1.6 to 3.9 µM. Compounds 1, 2, 7, and 8 showed significant synergistic activity against antibiotic-resistant Staphylococcus aureus strains.
Assuntos
Goniothalamus , Casca de Planta , Pironas , Goniothalamus/química , Pironas/química , Pironas/farmacologia , Pironas/isolamento & purificação , Estrutura Molecular , Estereoisomerismo , Casca de Planta/química , Humanos , Distribuição Contracorrente/métodos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificaçãoRESUMO
Objective: The meta-analysis was performed to evaluate the effectiveness of telemedicine interventions on patients with diabetic foot ulcers (DFU). Approach: The authors conducted a comprehensive search across eight databases. The aim was to identify randomized controlled trials examining the effectiveness of telemedicine for patients with DFU. Methodological qualities of included studies were assessed using Cochrane Handbook for Systematic Reviews of Intervention. Subsequently, a meta-analysis was conducted using RevMan 5.3 to synthesize the findings. Results: Ten studies involving 1,678 patients with DFU were included in the meta-analysis. In comparison to the face-to-face intervention group, telemedicine interventions significantly reduced the amputation rate (risk ratio = 0.64, 95% confidence interval [CI] = 0.44-0.92, p = 0.02), decreased costs (mean difference [MD] = -4158.51, 95% CI = -7304.69 to -1012.34, p = 0.01), better controlled fasting blood glucose (MD = -0.89, 95% CI = -1.43 to -0.36, p = 0.001), and achieved superior glycated hemoglobin control (MD = -0.71, 95% CI = -1.01 to -0.41, p < 0.00001). No significant differences were observed between the telemedicine group and the face-to-face group in terms of healing rate, mortality, and healing time. Innovations: Our study suggests that telemedicine is a viable strategy for managing DFU. Conclusions: The meta-analysis indicates that telemedicine interventions have a positive effect on DFU. Nevertheless, more well-designed and high-quality studies are needed to reach a conclusion with greater confidence.
RESUMO
Signal transduction pathways mediated by sensor histidine kinases and cognate response regulators control a variety of physiological processes in response to environmental conditions in most bacteria. Comparatively little is known about the mechanism(s) by which single-domain response regulators (SD-RRs), which lack a dedicated output domain but harbour a phosphoryl receiver domain, exert their various regulatory effects in bacteria. Here we have examined the role of the SD-RR proteins encoded by the phytopathogen Xanthomonas campestris pv. campestris (Xcc). We describe the identification and characterization of a SD-RR protein named McvR (motility, chemotaxis, and virulence-related response regulator) that is required for virulence and motility regulation in Xcc. Deletion of the mcvR open reading frame caused reduced motility, chemotactic movement, and virulence in Xcc. Global transcriptome analyses revealed the McvR had a broad regulatory role and that most motility and pathogenicity genes were down-regulated in the mcvR mutant. Bacterial two-hybrid and protein pull-down assays revealed that McvR did not physically interact with components of the bacterial flagellum but interacts with other SD-RR proteins (like CheY) and the subset of DNA-binding proteins involved in gene regulation. Site-directed mutagenesis and phosphor-transfer experiments revealed that the aspartyl residue at position 55 of the receiver domain is important for phosphorylation and the regulatory activity of McvR protein. Taken together, the findings describe a previously unrecognized class of SD-RR protein that contributes to the regulation of motility and virulence in Xcc.
Assuntos
Xanthomonas campestris , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Plantas/metabolismo , Virulência/genéticaRESUMO
Xanthomonas campestris pv. campestris (Xcc) controls virulence and plant infection mechanisms via the activity of the sensor kinase and response regulator pair HpaS/hypersensitive response and pathogenicity G (HrpG). Detailed analysis of the regulatory role of HpaS has suggested the occurrence of further regulators besides HrpG. Here we used in vitro and in vivo approaches to identify the orphan response regulator VemR as another partner of HpaS and to characterize relevant interactions between components of this signalling system. Bacterial two-hybrid and protein pull-down assays revealed that HpaS physically interacts with VemR. Phos-tag SDS-PAGE analysis showed that mutation in hpaS reduced markedly the phosphorylation of VemR in vivo. Mutation analysis reveals that HpaS and VemR contribute to the regulation of motility and this relationship appears to be epistatic. Additionally, we show that VemR control of Xcc motility is due in part to its ability to interact and bind to the flagellum rotor protein FliM. Taken together, the findings describe the unrecognized regulatory role of sensor kinase HpaS and orphan response regulator VemR in the control of motility in Xcc and contribute to the understanding of the complex regulatory mechanisms used by Xcc during plant infection.