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1.
Plants (Basel) ; 13(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38202452

RESUMO

The aim of this study was to investigate the impact of water and nitrogen regulation on the characteristics of water and fertilizer demands and the yield, quality, and efficiencies of the water and nitrogen utilization of peanuts cultivated under mulched drip irrigation in a desert-oasis region. The experiment, conducted in Urumqi, Xinjiang, centered on elucidating the response mechanisms governing peanut growth, yield, quality, water consumption patterns, and fertilizer characteristics during the reproductive period under the influence of water and nitrogen regulation. In the field experiments, three irrigation levels were implemented, denoted as W1 (irrigation water quota of 22.5 mm), W2 (irrigation water quota of 30 mm), and W3 (irrigation water quota of 37.5 mm). Additionally, two nitrogen application levels, labeled N1 (nitrogen application rate of 77.5 kg·ha-1) and N2 (a nitrogen application rate of 110 kg·ha-1), were applied, resulting in seven treatments. A control treatment (CK), which involved no nitrogen application, was also included in the experimental design. The results indicate a direct correlation between the increment in the irrigation quota and increases in farmland water-related parameters, including water consumption, daily water consumption intensity, and water consumption percentage. The nitrogen harvest index (NHI) demonstrated a higher value in the absence of nitrogen application compared to the treatment with elevated nitrogen levels. The application of nitrogen resulted in an elevation in both nitrogen accumulation and nitrogen absorption efficiency within pods and plants. When subjected to identical nitrogen application conditions, irrigation proved to be advantageous in enhancing water-use efficiency (WUE), nitrogen partial factor productivity (NPFP), and the yield of peanut pods. The contribution rate of water to pod yield and WUE exceeded that of nitrogen, while the contribution rate of nitrogen to nitrogen-use efficiency (NUE) was higher. The total water consumption for achieving a high yield and enhanced water- and nitrogen-use efficiencies in peanuts cultivated under drip irrigation with film mulching was approximately 402.57 mm. Taking into account yield, quality, and water- and nitrogen-used efficiencies, the use of an irrigation quota of 37.5 mm, an irrigation cycle of 10-15 days, and a nitrogen application rate of 110 kg·ha-1 can be regarded as an appropriate water and nitrogen management approach for peanut cultivation under mulched drip irrigation in Xinjiang.

2.
Biophys Rep ; 9(3): 159-175, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38028152

RESUMO

83 Structures of human nNOS, 55 structures of human eNOS, 13 structures of iNOS, and about 126 reported NOS-bound compounds are summarized and analyzed. Structural and statistical analysis show that, at least one copy of each analyzed compound binds to the active site (the substrate arginine binding site) of human NOS. And binding features of the three isoforms show differences, but the binding preference of compounds is not in the way helpful for inhibitor design targeting nNOS and iNOS, or for activator design targeting eNOS. This research shows that there is a strong structural and functional similarity between oxygenase domains of human NOS isoforms, especially the architecture, residue composition, size, shape, and distribution profile of hydrophobicity, polarity and charge of the active site. The selectivity and efficacy of inhibitors over the rest of isoforms rely a lot on chance and randomness. Further increase of selectivity via rational improvement is uncertain, unpredictable and unreliable, therefore, to achieve high selectivity through targeting this site is complicated and requires combinative investigation. After analysis on the current two targeting sites in NOS, the highly conserved arginine binding pocket and H4B binding pocket, new potential drug-targeting sites are proposed based on structure and sequence profiling. This comprehensive analysis on the structure and interaction profiles of human NOS and bound compounds provides fresh insights for drug discovery and pharmacological research, and the new discovery here is practically applied to guide protein-structure based drug discovery.

3.
Plants (Basel) ; 12(19)2023 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-37836108

RESUMO

The optimization of irrigation and fertilization indexes for peanuts with drip irrigation is urgently needed in Xinjiang. A field experiment was conducted during the 2021 peanut growing season at Urumqi, Xinjiang, in Northwestern China, to evaluate the effects of different water and nitrogen treatments on the growth, yield, and water and nitrogen utilization of peanuts. In field experiments, we set up three irrigation levels (irrigation water quotas of 22.5, 30, and 37.5 mm, respectively, for W1, W2, and W3), two nitrogen application levels (77.5 and 110 kg·ha-1, recorded as N1 and N2), and a control treatment (W2N0) that did not include the application of nitrogen. The results showed that nitrogen application enhanced the growth, physiological indexes, yield, and water use efficiency of the W1, W2, and W3 treatments when the irrigation volume remained the same. In comparison with no nitrogen application (W2N0), the peanut growth, physiological indexes, yield, and water use efficiency improved with increasing irrigation amounts in the N1 and N2 treatments. With an increase in the irrigation volume, the water use efficiency grew; the W3N2 treatment had the highest water use efficiency, which was 1.32 kg·m-3. The total water consumption and reproductive-stage water consumption of the peanuts in all treatments increased with the irrigation volume, and a high yield was achieved at 402.57 mm, which was 5.2974 Mg·ha-1. In the W1, W2, and W3 treatments, the nitrogen partial factor productivity significantly decreased as the nitrogen application increased, with the nitrogen partial factor productivity in the W3N1 treatment being the highest, at 60.61 kg·kg-1. A comprehensive evaluation based on principal component analysis assigned W3N2 the higher score. These findings suggest that irrigation water quotas of 37.5 mm should be coupled with 110 kg·ha-1 nitrogen applications for peanuts using drip irrigation in mulch film in Xinjiang.

4.
Cell Biochem Biophys ; 81(4): 577-597, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37624574

RESUMO

F-box proteins are involved in multiple cellular processes through ubiquitylation and consequent degradation of targeted substrates. Any significant mutation in F-box protein-mediated proteolysis can cause human malformations. The various cellular processes F-box proteins involved include cell proliferation, apoptosis, invasion, angiogenesis, and metastasis. To target F-box proteins and their associated signaling pathways for cancer treatment, researchers have developed thousands of F-box inhibitors. The most advanced inhibitor of FBW7, NVD-BK M120, is a powerful P13 kinase inhibitor that has been proven to bring about apoptosis in cancerous human lung cells by disrupting levels of the protein known as MCL1. Moreover, F-box Inhibitors have demonstrated their efficacy for treating certain cancers through targeting particular mutated proteins. This paper explores the key studies on how F-box proteins act and their contribution to malignancy development, which fabricates an in-depth perception of inhibitors targeting the F-box proteins and their signaling pathways that eventually isolate the most promising approach to anti-cancer treatments.


Assuntos
Proteínas F-Box , Neoplasias , Humanos , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Proteína 7 com Repetições F-Box-WD/genética , Proteína 7 com Repetições F-Box-WD/metabolismo , Proteínas de Ciclo Celular/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proteólise
5.
Biomed Pharmacother ; 157: 113934, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36395607

RESUMO

It has been proven that metastatic recurrence and therapeutic resistance are linked. Due to the variability of individuals and tumors, as well as the tumor's versatility in avoiding therapies, therapy resistance is more difficult to treat. Therapy resistance has significantly restricted the clinical feasibility and efficacy of tumor therapy, despite the discovery of novel compounds and therapy combinations with increasing efficacy. In several tumors, lysine specific demethylase 1 (LSD1) has been associated to metastatic recurrence and therapeutic resistance. For researchers to better comprehend how LSD1-mediated tumor therapy resistance occurs and how to overcome it in various tumors, this study focused on the role of LSD1 in tumor recurrence and therapeutic resistance. The importance of therapeutically targeted LSD1 was also discussed. Most gene pathway signatures are related to LSD1 inhibitor sensitivity. However, some gene pathway signatures, especially in AML, negatively correlate with LSD1 inhibitor sensitivity, but targeting LSD1 makes the therapy-resistant tumor sensitive to physiological doses of conventional therapy. We propose that combining LSD1 inhibitor with traditional tumor therapy can help patients attain a complete response and prevent cancer relapse.


Assuntos
Histona Desmetilases , Lisina , Humanos , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Recidiva Local de Neoplasia/genética , Imunoterapia , Epigenômica
6.
Eur J Med Chem ; 240: 114564, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35820351

RESUMO

LSD1 was significantly over-expressed in several cancer types, and its aberrant overexpression was revealed to play a crucial role in the initiation and progression of cancer. Several LSD1 inhibitors that were discovered and developed so far were found to be effective in attenuating tumor growth in both in vivo and in vitro studies. However, the major challenge associated with the development of cancer therapies is personalized treatment. Therefore, it is essential to look in detail at how LSD1 plays its part in carcinogenesis and whether there are any different expression levels of LSD1 in different tumors. Here in this review, fresh insight into a list of function correlated LSD1 binding proteins are provided, and we tried to figure out the role of LSD1 in different cancer types, including hematological malignancies and solid tumors. A critical description of mutation preference for LSD1 in different tumors was also discussed. Recent research findings clearly showed that the abrogation of LSD1 demethylase activity via LSD1 inhibitors markedly reduced the growth of cancer cells. But there are still many ambiguities regarding the role of LSD1 in different cancers. Therefore, targeting LSD1 for treating different cancers is still reductionist, and many challenges need to be met to improve the therapeutic outcomes of LSD1 inhibitors.


Assuntos
Histona Desmetilases , Neoplasias , Carcinogênese , Humanos , Neoplasias/tratamento farmacológico
7.
Mol Biol Rep ; 49(2): 1537-1544, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35025031

RESUMO

The F-box proteins (FBP), substrate recognition subunit of the SCF (Skp1-Cullin1-F-box protein complex) E3 ligase, play important roles in the ubiquitylation and subsequent degradation of the target proteins from several cellular processes. Disorders of F-box protein-mediated proteolysis lead to human malignancies. FBP plays an important role in many cellular processes, including cell proliferation, cell cycle, apoptosis, migration, invasion, and metastasis, suggesting that it can be associated with tumorigenesis, cancer development and progression. However, the expression and function of FBXO9 (F-box only protein 9) differ in various types of human cancer. Due to the ability to regulate the stability and activity of oncogenes and tumor-suppressor genes, and the physiological functions of many of the F-box proteins remain subtle, further genetic and mechanistic studies will elaborate and help define FBXO9's role. Targeting F-box protein or F-box protein signaling pathways could be an effective strategy for preventing or treating human cancer. This review is presented to summarize the part of FBXO9 in different types of human cancer and its regulation mechanism, and to pave the way to design FBXO9-targeting anticancer therapies.


Assuntos
Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Neoplasias/metabolismo , Apoptose/genética , Carcinogênese/genética , Ciclo Celular , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Proteínas F-Box/fisiologia , Humanos , Neoplasias/genética , Neoplasias/fisiopatologia , Proteólise , Transdução de Sinais/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
8.
Cancer Control ; 28: 10732748211051557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34802287

RESUMO

BACKGROUND: Numerous studies on the prognostic significance of lysine-specific demethylase 1 (LSD1) up-regulation in tumors have different outcomes. The inconsistency originated from various studies looking into the association between LSD1 and tumor cells has prompted the decision of this quantitative systematic review to decipher how up-regulated LSD1 and overall survival (OS) or recurrence-free survival (RFS) or disease-free survival (DFS) are linked in tumor patients. METHODS: Articles were searched from online databases such as Embase, Web of Science Core, PubMed, Google Scholar, and Scopus. The extraction of the hazard ratios (HR) with their 95% confidence intervals (CIs) was attained and survival data of 3151 tumor patients from 17 pieces of related research were used for this meta-analysis. RESULTS: To shed light on the link between LSD1 up-regulation and the prognosis of diverse tumors, the pooled hazard ratios (HRs) with their 95% confidence intervals (CIs) were determined. In this meta-analysis, it was observed that LSD1 up-regulation is linked with poor OS (HR = 2.08, 95% CI: 1.66-2.61, P < .01) and RFS (HR = 3.09, 95% CI: 1.81-5.26, P < .01) in tumor patients. However, LSD1 up-regulation was not linked to DFS (HR = 1.49, 95% CI: .83-2.69, P = .18) in tumor patients. The subcategory examination grouped by tumor type and ethnicity showed that LSD1 up-regulation was linked with a poor outcome in the esophageal tumor and hepatocellular carcinoma and Asian patients, respectively. For clinical-pathological factors, up-regulated LSD1 was significantly linked with Lymph node status. CONCLUSION: Despite the shortfall of the present work, this meta-analysis proposes that LSD1 up-regulation may be a prognostic biomarker for patients with tumors including esophageal tumors and hepatocellular carcinoma. We propose that large-scale studies are vital to substantiate these outcomes.


Assuntos
Biomarcadores Tumorais/genética , Histona Desmetilases/metabolismo , Neoplasias/genética , Neoplasias/mortalidade , Adolescente , Adulto , Idoso , Povo Asiático/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Criança , Progressão da Doença , Intervalo Livre de Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Regulação para Cima/genética , Adulto Jovem
9.
Neurosci Biobehav Rev ; 131: 59-76, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34536462

RESUMO

Chronic pain is a worldwide health problem, Acceptance and Commitment Therapy (ACT) is regarded as one of the promising interventions. ACT aims to help chronic pain patients to create space for pursuing valued life activities in spite of pain. This systematic review of randomized controlled trials (RCTs) examined the efficacy of ACT on functioning for chronic pain. Literature search was performed among seven databases, and 12 RCTs were retrieved. The revised Cochrane risk of bias tool (RoB 2.0) was employed to assess the quality of the 12 RCTs, of which 10 were rated as "low risks", and 2 as "some concerns". Effect sizes of single RCTs and the pooled effect sizes of meta analyses were all rated by Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Low to moderate evidence showed that ACT played a positive immediate role in functioning for patients with chronic pain; however, it is inconsistent whether the effect can be sustained. More RCTs are warranted within specific chronic pain conditions.


Assuntos
Terapia de Aceitação e Compromisso , Dor Crônica , Doença Crônica , Dor Crônica/terapia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Oncol ; 2021: 5512524, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33833800

RESUMO

Tumors are the foremost cause of death worldwide. As a result of that, there has been a significant enhancement in the investigation, treatment methods, and good maintenance practices on cancer. However, the sensitivity and specificity of a lot of tumor biomarkers are not adequate. Hence, it is of inordinate significance to ascertain novel biomarkers to forecast the prognosis and therapy targets for tumors. This review characterized LSD1 as a biomarker in different tumors. LSD1 inhibitors in clinical trials were also discussed. The recent pattern advocates that LSD1 is engaged at sauce chromatin zones linking with complexes of multi-protein having an exact DNA-binding transcription factor, establishing LSD1 as a favorable epigenetic target, and also gives a large selection of therapeutic targets to treat different tumors. This review sturdily backing the oncogenic probable of LSD1 in different tumors indicated that LSD1 levels can be used to monitor and identify different tumors and can be a useful biomarker of progression and fair diagnosis in tumor patients. The clinical trials showed that inhibitors of LSD1 have growing evidence of clinical efficacy which is very encouraging and promising. However, for some of the inhibitors such as GSK2879552, though selective, potent, and effective, its disease control was poor as the rate of adverse events (AEs) was high in tumor patients causing clinical trial termination, and continuation could not be supported by the risk-benefit profile. Therefore, we propose that, to attain excellent clinical results of inhibitors of LSD1, much attention is required in designing appropriate dosing regimens, developing in-depth in vitro/in vivo mechanistic works of LSD1 inhibitors, and developing inhibitors of LSD1 that are reversible, safe, potent, and selective which may offer safer profiles.

11.
Tob Induc Dis ; 19: 13, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642967

RESUMO

INTRODUCTION: The health hotline (12320) of Shanghai, not only offers residents information about health knowledge, policies and regulations, but also serves as a channel for public supervision on health issues. This study explored the content of calls towards the Shanghai health hotline (SHH) related to e-cigarettes. METHODS: The call sheets related to e-cigarette received by SHH were collected from 2014 to 2019. Voice conversations were recorded by the management system of SHH and the telephone operators then converted the recordings into text to collect the information of residents. We used a natural language processor, ROST-CM6.0 to clean up and create words dictionaries and analyzed the text using a text-mining method to identify themes and other useful details. RESULTS: Among the 491 call sheets, 87.4% were for consultation and 7.5% for complaint. The issue that Shanghai citizens were concerned about most was 'whether the e-cigarette belongs to the jurisdictional scope of the Amendment', and 76.6% of the call sheets were related to this particular concern. Other concerns were 'whether e-cigarettes are harmful or not' (9.4%), 'can e-cigarettes help people quit smoking or have side effects' (6.1%), 'whether e-cigarettes can be sold openly in shopping malls and where can we buy e-cigarettes' (2.2%) and 'can minors buy e-cigarettes' (1.0%). CONCLUSIONS: The number of call sheets about e-cigarettes received by SHH has seen a significant increase since the Amendment was implemented with questions primarily focused on 'if electronic cigarettes belong to the scope of tobacco control'.

12.
J Adv Nurs ; 77(1): 417-426, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33058238

RESUMO

AIM: To explore the efficacy of acceptance and commitment therapy (ACT) on chronic pain in terms of functioning; and to identify the most promising modes and patterns for implementing ACT. DESIGN: Systematic review and meta-analysis. METHODS: We will include randomized controlled trials which focus on the efficacy of ACT on chronic pain conditions with functioning as the primary outcome. Seven databases have been searched and grey literature will also be systematically searched for. Eligible studies will be screened. The newly revised Cochrane risk of bias tool will be used to assess the quality of the included studies. Data will be extracted, and meta-analyses will be performed within specific condition groups of chronic pain. Meta-regression and subgroup analyses will be employed to identify the efficacious modes and patterns for implementing the therapy. Grading of Recommendations Assessment, Development, and Evaluation approach will be applied to reach a convincing conclusion. The study has been funded since July 2018. DISCUSSION: This systematic review aims to explore the efficacy of ACT for chronic pain on functioning based on the latest evidence. The most promising manners will be identified for designing and delivering the therapy. An accurate, transparent, and standardized review process is expected by adhering to the instructions of relevant guidelines. IMPACT: Chronic pain is prevalent worldwide and reduced functioning is one of the leading consequences. With the anticipated evidence of high level, this research attempts to examine the role of acceptance and commitment therapy, a promising psychological intervention, in the management of chronic pain for improving individual's functioning status. The systematic review may contribute to a more convincing and targeted conclusion compared with the existing studies of its kind.


Assuntos
Terapia de Aceitação e Compromisso , Dor Crônica , Dor Crônica/terapia , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
13.
Int J Nurs Stud ; 106: 103507, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32320936

RESUMO

BACKGROUND: Globally, more than half a billion people are suffering from chronic low back pain, which results in poor quality of life for patients and major welfare cost for society. Currently, e-Health has been considered as a potential strategy to deliver self-management programs for chronic low back pain, but its effects are uncertain. OBJECTIVES: To assess the efficacy on pain intensity and disability of e-Health based self-management programs on chronic low back pain. DESIGN: Systematic review and meta-analysis DATA SOURCES: Searches of Pubmed, the Cochrane Library, Web of Science, Cumulative Index of Nursing and Allied Health Literature, Elsevier, Physiotherapy Evidence Database and ProQuest from inception through 2nd April 2019. REVIEW METHODS: Randomized controlled trials were screened and selected if they examined e-Health based self-management programs on chronic low back pain and assessed pain intensity and disability as primary outcomes. Risks of bias were assessed by two independent reviewers. Evidence quality was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Meta-analyses were performed to investigate the effects of e-Health based self-management programs on pain intensity and disability for chronic low back pain. Subgroup analyses were conducted. RESULTS: Eight randomized controlled trials were included. For pain intensity, moderate-quality evidence indicated there was a clinically important effect of e-Health based self-management programs for relieving pain both at immediate and short-term follow-ups. For disability, moderate-quality evidence showed there was a clinically important effect of e-Health based self-management programs for improving disability at immediate follow-up, and low-quality of evidence showed no significant difference at short-term follow-ups, but with a favorable trend. The results of subgroup analyses indicated that m-Health based self-management programs showed better immediate effects on both pain and disability than web-Health based programs, and programs with durations ≤ 8 weeks demonstrated a better immediate effect on pain than those with durations >8 weeks, but not on disability. CONCLUSIONS: Generally, e-Health based self-management programs may play a positive role in improving pain and disability within short-term period for chronic low back pain patients. More rigorous trials are warranted to determine the optimal delivery mode, duration, and long-term effect of e-Health based self-management programs.


Assuntos
Dor Lombar/terapia , Autoeficácia , Autogestão/métodos , Telemedicina/normas , Humanos , Dor Lombar/complicações , Dor Lombar/psicologia , Manejo da Dor/psicologia , Manejo da Dor/normas , Medição da Dor/métodos , Autogestão/psicologia , Telemedicina/métodos
14.
Pain Pract ; 19(5): 510-521, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30739397

RESUMO

BACKGROUND: Chronic low back pain (CLBP) has become a worldwide health concern, and emotional distress is an important issue for CLBP management. However, it remains poorly understood how emotional distress happens and develops. This study aimed to systematically explore the correlates of emotional distress in patients with CLBP. METHODS: The study was a multisite, cross-sectional survey with a sample of 252 patients with CLBP in urban communities. A battery of questionnaires was used to collect data. Univariate analysis, Pearson correlation analysis, and hierarchical linear regression analysis were performed. RESULTS: The mean score of emotional distress among 252 patients with CLBP was 13.85 ± 6.50. Hierarchical regression analysis indicated that the demographic factors, psychobehavioral factors, and social support of patients with CLBP were associated with their emotional distress, uniquely explaining 16.5%, 18.4%, and 6.2% of the variance, respectively. Five factors were found to be associated with patients' emotional distress: pain intensity (ß = 0.257, P < 0.001), passive coping (ß = 0.297, P < 0.001), active coping (ß = -0.254, P < 0.001), self-efficacy (ß = -0.155, P = 0.005), and social support (ß = -0.268, P < 0.001). CONCLUSIONS: Patients with CLBP suffered from clinically significant emotional distress. Patients' demographics, psychobehavioral factors, and social support were all related to emotional distress. The findings help us to identify the characteristics of patients with CLBP at high risk for emotional distress and to formulate corresponding countermeasures. LAY SUMMARY: This study aimed to explored the correlates of emotional distress of patients with chronic low back pain (CLBP) by hierarchical linear regression analysis. The study found that patients' demographic factors, psycho-behavioral factors, and social support were associated with their emotional distress, uniquely explaining 16.5%, 18.4%, and 6.2% of the variance, respectively. Pain intensity, passive coping, active coping, self-efficacy, and social support were detected as significant correlates.


Assuntos
Dor Lombar/psicologia , Angústia Psicológica , Adaptação Psicológica , Adulto , Estudos Transversais , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Autoeficácia , Apoio Social
15.
J Mol Biol ; 430(21): 4183-4194, 2018 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-30121296

RESUMO

The accurate modification of the tRNAIle anticodon wobble cytosine 34 is critical for AUA decoding in protein synthesis. Archaeal tRNAIle2 cytosine 34 is modified with agmatine in the presence of ATP by TiaS (tRNAIle2 agmatidine synthetase). However, no structure of apo-form full-length TiaS is available currently. Here, the crystal structures of apo TiaS and a complex of TiaS-agmatine-AMPPCP-Mg are presented, with properly folded zinc ribbon and Cys4-zinc coordination identified. Compared with tRNAIle2-bound form, the architecture of apo TiaS shows a totally different conformation of zinc ribbon. Molecular dynamics simulations of the docking complex between free-state TiaS and tRNAIle2 suggest that zinc ribbon domain is capable of performing large-scale motions to sample substrate binding-competent conformation. Principle component analysis and normal mode analysis show consistent results about the relative directionality of functionally correlated zinc ribbon motions. Apo TiaS and TiaS-agmatine-AMPPCP-Mg/TiaS-AMPCPP-Mg complex structures capture two snapshots of the flexible ATP-Mg binding p2loop step-by-step stabilization. Research from this study provides new insight into TiaS functional mechanism and the dynamic feature of zinc ribbons.


Assuntos
Aminoacil-tRNA Sintetases/química , Modelos Moleculares , Conformação Molecular , Zinco/química , Aminoacil-tRNA Sintetases/metabolismo , Catálise , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Relação Estrutura-Atividade , Especificidade por Substrato , Zinco/metabolismo
16.
IUCrJ ; 5(Pt 4): 510-518, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30002851

RESUMO

There are few cases where tyrosine has been shown to be involved in catalysis or the control of catalysis despite its ability to carry out chemistry at much higher potentials (1 V versus NHE). Here, it is shown that a tyrosine that blocks the hydrophobic substrate-entry channel in copper-haem nitrite reductases can be activated like a switch by the treatment of crystals of Ralstonia pickettii nitrite reductase (RpNiR) with nitric oxide (NO) (-0.8 ± 0.2 V). Treatment with NO results in an opening of the channel originating from the rotation of Tyr323 away from AspCAT97. Remarkably, the structure of a catalytic copper-deficient enzyme also shows Tyr323 in the closed position despite the absence of type 2 copper (T2Cu), clearly demonstrating that the status of Tyr323 is not controlled by T2Cu or its redox chemistry. It is also shown that the activation by NO is not through binding to haem. It is proposed that activation of the Tyr323 switch is controlled by NO through proton abstraction from tyrosine and the formation of HNO. The insight gained here for the use of tyrosine as a switch in catalysis has wider implications for catalysis in biology.

17.
Pain Pract ; 18(6): 736-747, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29171174

RESUMO

BACKGROUND: As a bio-psycho-social issue, chronic low back pain (CLBP) has been a significant topic in health management, and patients' quality of life (QOL) is gaining extensive attention. Self-efficacy, pain fear-avoidance belief (FAB), and coping styles play important roles in the QOL of CLBP patients. However, it remains unclear how self-efficacy and FAB influence QOL through specific coping styles. This study aimed to explore the influencing paths of self-efficacy, FAB, and coping styles on the QOL of patients with CLBP. METHODS: This study relies on a multisite, cross-sectional design involving 221 CLBP patients. Stepwise multiple regression and structural equation modeling were employed. RESULTS: CLBP patients lived with a poor global QOL. Self-efficacy played a direct, positive role in predicting QOL for patients with CLBP (ß = 0.35), and it also played an indirect, positive role in predicting QOL (ß = 0.19) through active coping styles (ß = 0.31). FAB played a direct, negative role in predicting QOL (ß = -0.33), and it also played an indirect, negative role in predicting QOL (ß = -0.32) through passive coping styles (ß = 0.32). CONCLUSIONS: Self-efficacy and FAB are both directly and indirectly related to global QOL, and coping styles are important mediating variables. Self-efficacy and active coping are protective factors for the QOL of CLBP patients, while FAB and passive coping are risk factors. Health education strategies are recommended by medical personnel to enhance CLBP patients' pain self-efficacy, decrease pain FAB, and modify pain coping styles, so that their global QOL can be improved.


Assuntos
Adaptação Psicológica , Medo/psicologia , Dor Lombar/psicologia , Qualidade de Vida , Autoeficácia , Adulto , Povo Asiático , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada
18.
Patient Educ Couns ; 100(1): 37-49, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27554077

RESUMO

OBJECTIVE: To determine the effectiveness of self-management programs (SMPs) on chronic low back pain (CLBP). METHODS: A search of randomized controlled trials (RCTs) was performed in Pubmed, Cochrane Library, Web of Science, Elsevier, and CINAHL through June, 2015. Two reviewers selected trials, conducted critical appraisal, and extracted data. Meta analyses were performed. RESULTS: Thirteen moderate-quality RCTs were included. There were 9 RCTs for immediate post intervention on pain intensity and disability, 5 RCTs for short term, 3 RCTs for intermediate and 4 RCTs for long term. Specifically, the effect sizes (ESs) of SMP on pain intensity were -0.29, -0.20, -0.23, and -0.25 at immediate post-intervention, short-term, intermediate-term, and long-term follow-ups, respectively. The ESs on disability were -0.28, -0.23, -0.19, and -0.19 at immediate post-intervention, short-term, intermediate-term, and long-term follow-ups, respectively. CONCLUSION: For CLBP patients, there is moderate-quality evidence that SMP has a moderate effect on pain intensity, and small to moderate effect on disability. PRACTICE IMPLICATIONS: SMP can be regarded as an effective approach for CLBP management. In addition to face-to-face mode, internet-based strategy can also be considered as a useful option to deliver SMP. Theoretically driven programs are preferred.


Assuntos
Dor Crônica/terapia , Dor Lombar/terapia , Manejo da Dor , Autocuidado/métodos , Autogestão , Humanos , Dor Lombar/diagnóstico , Dor Lombar/psicologia , Autocuidado/psicologia
19.
PLoS One ; 11(8): e0160409, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27552099

RESUMO

Maternal deprivation (MD) is frequently used as an early life stress model in rodents to investigate behavioral and neurological responses under stressful conditions. However, the effect of MD on the early postnatal development of rodents, which is when multiple neural systems become established, is rarely investigated due to methodological limitations. Ultrasonic vocalizations (USVs) are one of the few responses produced by neonatal rodents that can be quantitatively analyzed, and the quantification of USVs is regarded as a novel approach to investigate possible alterations in the neurobehavioral and emotional development of infant rodents under stress. To investigate the effect of MD on pup mice, we subjected C57BL/6J mice to MD and recorded the USVs of pups on postnatal days 1, 3, 7, 8, and 14. To determine whether the effect of MD on USVs was acute or cumulative, pre- and post-separation USV groups were included; sex differences in pup USV emission were also investigated. Our results suggest that (i) USV activity was high on postnatal days 3-8; (ii) the MD effect on USVs was acute, and a cumulative effect was not found; (iii) the MD mice vocalized more and longer than the controls at a lower frequency, and the effect was closely related to age; and (iv) female pups were more susceptible than males to the effect of MD on USV number and duration between postnatal days 3-8.


Assuntos
Comportamento Animal/fisiologia , Privação Materna , Estresse Psicológico , Vocalização Animal/fisiologia , Animais , Animais Recém-Nascidos/fisiologia , Emoções/fisiologia , Feminino , Camundongos , Ultrassom
20.
Chem Sci ; 6(7): 3881-3885, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26417427

RESUMO

While nature employs various covalent and non-covalent strategies to modulate tyrosine (Y) redox potential and pK a in order to optimize enzyme activities, such approaches have not been systematically applied for the design of functional metalloproteins. Through the genetic incorporation of 3-methoxytyrosine (OMeY) into myoglobin, we replicated important features of cytochrome c oxidase (CcO) in this small soluble protein, which exhibits selective O2 reduction activity while generating a small amount of reactive oxygen species (ROS). These results demonstrate that the electron donating ability of a tyrosine residue in the active site is important for CcO function. Moreover, we elucidated the structural basis for the genetic incorporation of OMeY into proteins by solving the X-ray structure of OMeY specific aminoacyl-tRNA synthetase complexed with OMeY.

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