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BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) inhibitors appear to benefit bone tissue in antihypertensive treatment. However, the association between RAAS inhibitors and bone metabolism was inconsistent. METHODS AND STUDY DESIGN: Based on the study of Risk Evaluation of Cancers in Chinese Diabetic Individuals(REACTION) conducted in 2011, We followed 6,252 Lanzhou residents aged 40-75 years from 2014 to 2016. Finally, 1,625 hypertension cases with complete data were included in the analysis. The study subjects were divided into four groups according to the type of antihypertensive drugs. We employed logistic or multivariate Cox proportional hazards regression to estimate the association between different antihypertensive drug use and osteoporosis, the risk of fracture, and the change in bone mineral density (BMD) level. The association of osteoporosis or the fracture risk by cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated. RESULTS: The cross-sectional study showed that there was no significant association between baseline antihypertensive drugs (angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB)) use and osteoporosis and fracture. During a mean follow-up of 3.4 years in the longitudinal study, there were 478 new osteoporosis cases and 76 fractures. Compared with patients without antihypertensive drug use, the hazard ratios (HRs) [95% confidence interval (CI)] for the risk of osteoporosis were 1.005(0.651,1.552) and 1.077(0.793,1.462) in ACEI or ARB use (p > 0.05). ACEI or ARB use was also not significantly associated with fracture risk (HR 1.102(0.326,3.726), 0.735(0.251,2.148), p > 0.05). Further analysis showed that the use of ACEI (HR 1.078(0.146,7.950)) or ARB (HR 1.169(0.347,3.939)) was not significantly associated with the improvement of osteoporosis (p > 0.05). In addition, the duration of RAAS inhibitors used showed no apparent correlation with the risk of osteoporosis (≤ 3 years: HR 0.872 (0.516, 1.474), > 3 years: HR 1.151 (0.574, 2.308)), nor with the improvement of osteoporosis and the risk of fracture. Meanwhile, the association mentioned above did not change compared to different RAAS inhibitors. CONCLUSIONS: The use of RAAS inhibitors, including ACEIs and ARBs, was not significantly associated with osteoporosis, risk of fracture, or BMD change.
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Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Densidade Óssea , Hipertensão , Osteoporose , Sistema Renina-Angiotensina , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Osteoporose/epidemiologia , Osteoporose/tratamento farmacológico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Idoso , China/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos Prospectivos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Adulto , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Sistema Renina-Angiotensina/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Estudos Transversais , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Fatores de Risco , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/induzido quimicamente , Estudos Longitudinais , Seguimentos , Medição de RiscoRESUMO
Given the multifaceted character of depression and its related symptoms, an adolescent living with it is at increased risk for a wide range of adverse events. This research aimed to understand and characterize the psychosocial rehabilitation experiences of depressed teenage participants in the Greater Accra Region of Ghana. A cross-sectional semi-structured interview design influenced by an interpretive phenomenological analysis (IPA) technique was adopted. We employed a nonprobability, purposeful sampling approach to recruit twenty-one adolescents (6 males, 15 females) diagnosed with depression from the community after one month of discharge from admission and undergoing psychosocial rehabilitation. Using separate interviews, we gathered and analyzed data using interpretive phenomenological analysis to produce themes and sub-themes. These were presented with the participants' direct quotations. We discovered that the perspectives of adolescents' psychosocial rehabilitation experience include hopelessness and suicide ideation, coping difficulties, undesirable attitudes from support networks, challenges related to school, and isolation. Participants suggested appropriate therapeutic environments, encouraging support systems, and the media's role in preventing and treating depression among young people as rehabilitation approaches that could assist adolescents to remain lucid for longer intervals. These results shed light on the tragic realities faced by depressed adolescents. There is an urgent need to put well-defined structures in place to aid their rehabilitation and develop coping strategies for a better life.
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BACKGROUND: Returning to school can be challenging for children and adolescents with cancer who have been absent for a long time. As there is little known about the return to school experience of children and adolescents with cancer, this meta-synthesis aimed to describe the experiences of children and adolescent cancer patients as they return to school. METHODS: Seven English databases and three Chinese databases were searched from inception to March 14, 2023. The Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) was used to appraise study quality. Data were synthesized using the Thomas and Harden thematic and content analysis method. RESULTS: Twelve qualitative studies met the inclusion criteria and were analyzed into meta-synthesis. Data synthesis led to constructing four analytical themes and twelve sub-themes. The four major themes constructed were:benefits to school re-entry, barriers to school re-entry, motivators to school re-entry and the adaptation process after returning to school. CONCLUSION: Children and adolescents with cancer were willing to return to education and can adapt to school life over time. But they were faced with challenges, including physical, psychological, and social barriers. Appropriate measures need to be taken to reduce those barriers. IMPLICATIONS TO PRACTICE: Findings can be used to inform future research and interventions to support a successful return to education for children and adolescents with cancer. Healthcare providers should address the needs of children and adolescents at different stages and actively work with schools, hospitals and families to help childhood cancer survivors successfully return to school.
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Neoplasias , Pesquisa Qualitativa , Humanos , Adolescente , Criança , Neoplasias/psicologia , Adaptação Psicológica , Feminino , Masculino , Instituições Acadêmicas , Sobreviventes de Câncer/psicologiaRESUMO
Aliphatic glucosinolates are an abundant group of plant secondary metabolites in Brassica vegetables, with some of their degradation products demonstrating significant anti-cancer effects. The transcription factors MYB28 and MYB29 play key roles in the transcriptional regulation of aliphatic glucosinolates biosynthesis, but little is known about whether BoMYB28 and BoMYB29 are also modulated by upstream regulators or how, nor their gene regulatory networks. In this study, we first explored the hierarchical transcriptional regulatory networks of MYB28 and MYB29 in a model plant, then systemically screened the regulators of the three BoMYB28 homologs in cabbage using a yeast one-hybrid. Furthermore, we selected a novel RNA binding protein, BoRHON1, to functionally validate its roles in modulating aliphatic glucosinolates biosynthesis. Importantly, BoRHON1 induced the accumulation of all detectable aliphatic and indolic glucosinolates, and the net photosynthetic rates of BoRHON1 overexpression lines were significantly increased. Interestingly, the growth and biomass of these overexpression lines of BoRHON1 remained the same as those of the control plants. BoRHON1 was shown to be a novel, potent, positive regulator of glucosinolates biosynthesis, as well as a novel regulator of normal plant growth and development, while significantly increasing plants' defense costs.
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Brassica , Regulação da Expressão Gênica de Plantas , Glucosinolatos , Proteínas de Plantas , Proteínas de Ligação a RNA , Fatores de Transcrição , Glucosinolatos/metabolismo , Brassica/metabolismo , Brassica/genética , Brassica/crescimento & desenvolvimento , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Redes Reguladoras de Genes , Plantas Geneticamente ModificadasRESUMO
BACKGROUND: Cancer-related fatigue (CRF) emerges as a common symptom in pediatric cancer patients during treatment. Exercise interventions are increasingly being used as CRF interventions to improve CRF in children with cancer. AIM: The objective of this meta-analysis was to synthesize the best available evidence concerning the effectiveness of exercise interventions for cancer-related fatigue in children with cancer. METHODS: Six databases were extensively searched from inception to December 2023 to identify relevant randomized controlled trials. The risk of bias and methodological quality were assessed using the Cochrane appraisal tool. Pooled effects were calculated using a random-effects model. Heterogeneity was assessed using the I2 test. RESULTS: Eight trials (n = 465) were finally included. Exercise was statistically more effective than conventional care in improving CRF in children with cancer (SMD = -0.62, 95% CI [-1.21, -0.03]) with high statistical heterogeneity (p = .004; I2 = 86%). The results of the subgroup analysis showed that intervention duration <12 weeks (p < .05), exercise frequency ≥ 3 times/week (p < .05), and exercise duration <45 min/time (p < .05) were more effective in improving CRF in children with cancer. LINKING EVIDENCE TO ACTION: Our results suggest that exercise interventions are effective in reducing CRF in children with cancer. We recommend exercise frequency ≥ 3 times/week, exercise duration <45 min/time, and intervention duration <12 weeks.
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BACKGROUND: Physical activity has been utilized as an effective strategy to prevent gestational diabetes mellitus (GDM). However, most pregnant women with high risk for GDM did not achieve the recommended physical activity level. Furthermore, relevant physical activity protocols have varied without theory-guided and evidence-based tailored to pregnant women with high risk for GDM. This study aimed to develop and pilot test a theory-guided and evidence-based physical activity intervention protocol for pregnant women with high risk for GDM. METHODS: The study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention (the MRC framework). The preliminary protocol for physical activity intervention was developed based on self-efficacy theory, research evidence identified from systematic reviews and clinic trials, stakeholder engagement, context, and economic considerations. The preliminary intervention protocol was validated through a content validity study by an expert panel of 10 experts. A single-blinded randomized controlled trial (RCT) was designed to test the feasibility and acceptability of the intervention. RESULTS: The validity of the preliminary intervention protocol was excellent as consensus was achieved. The final 13 sessions of self-efficacy enhancing physical activity intervention protocol were developed, including knowledge education, exercise clinic visits and video, and group discussions with face-to-face and online blended sessions. In the feasibility study, 34 pregnant women with high risk for GDM were randomized for the intervention (n = 17) or the control group (n = 17). The recruitment and retention rates were 82.9% and 58.9%, respectively. Women in the intervention group had a lower incidence of GDM (26.7% vs. 36.5%) than the control group (P >0.05). All participants were satisfied with the intervention and agreed that the intervention was helpful. CONCLUSIONS: The developed self-efficacy-enhancing physical activity intervention is a feasible and acceptable intervention for enhancing physical activity among pregnant women with high risk for GDM and is ready to be tested in a more extensive RCT study. TRIAL REGISTRATION: The study was registered on 4 February 2022 (ChiCTR2200056355) by the Chinese Clini Trial Registry (CHiCTR).
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Diabetes Gestacional , Feminino , Gravidez , Humanos , Diabetes Gestacional/prevenção & controle , Estudos de Viabilidade , Gestantes , Assistência Ambulatorial , Exercício FísicoRESUMO
In this Letter, we establish a new theoretical paradigm for vortex Majorana physics in the recently discovered topological iron-based superconductors (TFeSCs). While TFeSCs are widely accepted as an exemplar of topological insulators (TIs) with intrinsic s-wave superconductivity, our theory implies that such a common belief could be oversimplified. Our main finding is that the normal-state bulk Dirac nodes, usually ignored in TI-based vortex Majorana theories for TFeSCs, will play a key role of determining the vortex state topology. In particular, the interplay between TI and Dirac nodal bands will lead to multiple competing topological phases for a superconducting vortex line in TFeSCs, including an unprecedented hybrid topological vortex state that carries both Majorana bound states and a gapless dispersion. Remarkably, this exotic hybrid vortex phase generally exists in the vortex phase diagram for our minimal model for TFeSCs and is directly relevant to TFeSC candidates such as LiFeAs. When the fourfold rotation symmetry is broken by vortex-line tilting or curving, the hybrid vortex gets topologically trivialized and becomes Majorana free, which could explain the puzzle of ubiquitous trivial vortices observed in LiFeAs. The origin of the Majorana signal in other TFeSC candidates such as FeTe_{x}Se_{1-x} and CaKFe_{4}As_{4} is also interpreted within our theory framework. Our theory sheds new light on theoretically understanding and experimentally engineering Majorana physics in high-temperature iron-based systems.
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We establish quasi-two-dimensional thin films of iron-based superconductors (FeSCs) as a new high-temperature platform for hosting intrinsic time-reversal-invariant helical topological superconductivity (TSC). Based on the combination of Dirac surface state and bulk extended s-wave pairing, our theory should be directly applicable to a large class of experimentally established FeSCs, opening a new TSC paradigm. In particular, an applied electric field serves as a "topological switch" for helical Majorana edge modes in FeSC thin films, allowing for an experimentally feasible design of gate-controlled helical Majorana circuits. Applying an in-plane magnetic field drives the helical TSC phase into a higher-order TSC carrying corner-localized Majorana zero modes. Our proposal should enable the experimental realization of helical Majorana fermions.
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We show that Floquet chiral topological superconductivity arises naturally in Josephson junctions made of magnetic topological insulator-superconductor sandwich structures. The Josephson phase modulation associated with an applied bias voltage across the junction drives the system into the anomalous Floquet chiral topological superconductor hosting chiral Majorana edge modes in the quasienergy spectrum, with the bulk Floquet bands carrying zero Chern numbers. The bias voltage acts as a tuning parameter enabling novel Floquet topological quantum phase transitions driving the system into a myriad of exotic Majorana-carrying Floquet topological superconducting phases. Our theory establishes a new paradigm for realizing Floquet chiral topological superconductivity in solid-state systems, which should be experimentally directly accessible.
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Harsh environmental factors have continuous negative effects on plant growth and development, leading to metabolic disruption and reduced plant productivity and quality. However, filamentation temperature-sensitive H protease (FtsH) plays a prominent role in helping plants to cope with these negative impacts. In the current study, we examined the transcriptional regulation of the CaFtsH06 gene in the R9 thermo-tolerant pepper (Capsicum annuum L.) line. The results of qRT-PCR revealed that CaFtsH06 expression was rapidly induced by abiotic stress treatments, including heat, salt, and drought. The CaFtsH06 protein was localized to the mitochondria and cell membrane. Additionally, silencing CaFtsH06 increased the accumulation of malonaldehyde content, conductivity, hydrogen peroxide (H2O2) content, and the activity levels of superoxide dismutase and superoxide (·O2-), while total chlorophyll content decreased under these abiotic stresses. Furthermore, CaFtsH06 ectopic expression enhanced tolerance to heat, salt, and drought stresses, thus decreasing malondialdehyde, proline, H2O2, and ·O2- contents while superoxide dismutase activity and total chlorophyll content were increased in transgenic Arabidopsis. Similarly, the expression levels of other defense-related genes were much higher in the transgenic ectopic expression lines than WT plants. These results suggest that CaFtsH06 confers abiotic stress tolerance in peppers by interfering with the physiological indices through reducing the accumulation of reactive oxygen species, inducing the activities of stress-related enzymes and regulating the transcription of defense-related genes, among other mechanisms. The results of this study suggest that CaFtsH06 plays a very crucial role in the defense mechanisms of pepper plants to unfavorable environmental conditions and its regulatory network with other CaFtsH genes should be examined across variable environments.
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Capsicum/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Capsicum/genética , Secas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Estresse Fisiológico/genética , Estresse Fisiológico/fisiologiaRESUMO
Monolayer WTe_{2}, a centrosymmetric transition metal dichacogenide, has recently been established as a quantum spin Hall insulator and found superconducting upon gating. Here we study the pairing symmetry and topological nature of superconducting WTe_{2} with a microscopic model at mean-field level. Surprisingly, we find that the spin-triplet phases in our phase diagram all host Majorana modes localized on two opposite corners. Even when the conventional pairing is favored, we find that an intermediate in-plane magnetic field exceeding the Pauli limit stabilizes an unconventional equal-spin pairing aligning with the field, which also hosts Majorana corner modes. Motivated by our findings, we obtain a recipe for two-dimensional superconductors featuring "higher-order topology" from the boundary perspective. Generally, a superconducting inversion-symmetric quantum spin Hall material whose normal-state Fermi surface is away from high-symmetry points, such as gated monolayer WTe_{2}, hosts Majorana corner modes if the superconductivity is parity-odd. We further point out that this higher-order phase is an inversion-protected topological crystalline superconductor and study the bulk-boundary correspondence. Finally, we discuss possible experiments for probing the Majorana corner modes. Our findings suggest superconducting monolayer WTe_{2} is a playground for higher-order topological superconductivity and possibly the first material realization for inversion-protected Majorana corner modes without utilizing proximity effect.
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We propose MnBi_{2n}Te_{3n+1} as a magnetically tunable platform for realizing various symmetry-protected higher-order topology. Its canted antiferromagnetic phase can host exotic topological surface states with a Möbius twist that are protected by nonsymmorphic symmetry. Moreover, opposite surfaces hosting Möbius fermions are connected by one-dimensional chiral hinge modes, which offers the first material candidate of a higher-order topological Möbius insulator. We uncover a general mechanism to feasibly induce this exotic physics by applying a small in-plane magnetic field to the antiferromagnetic topological insulating phase of MnBi_{2n}Te_{3n+1}, as well as other proposed axion insulators. For other magnetic configurations, two classes of inversion-protected higher-order topological phases are ubiquitous in this system, which both manifest gapped surfaces and gapless chiral hinge modes. We systematically discuss their classification, microscopic mechanisms, and experimental signatures. Remarkably, the magnetic-field-induced transition between distinct chiral hinge mode configurations provides an effective "topological magnetic switch".
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This study aimed to investigate the relationships between cognitive emotion regulation (CER) strategies, resilience, and insomnia and the underlying mechanism that explains the relationships. Six hundred and fifty-three middle-aged and old people recruited from community service centers in Henan province completed questionnaires related to CER strategies, resilience, and insomnia. Results showed refocus on planning and positive reappraisal negatively predicted insomnia, and catastrophising, rumination and self-blame positively predicted insomnia. Moreover, maladaptive emotion regulation strategies (especially catastrophising) mediated the relationship between resilience and insomnia. The findings suggest the middle-aged and elderly with insomnia tended to employ maladaptive emotion regulation strategies and had lower resilience. Maladaptive emotion regulation strategies buffered the positive effect of resilience on sleep.
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Catastrofização/fisiopatologia , Regulação Emocional/fisiologia , Resiliência Psicológica , Ruminação Cognitiva/fisiologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Motivated by recent experiments on FeTe_{1-x}Se_{x}, we construct an explicit minimal model of an iron-based superconductor with band inversion at the Z point and nontopological bulk s_{±} pairing. While there has been considerable interest in Majorana zero modes localized at vortices in such systems, we find that our model-without any vortices-intrinsically supports 1D helical Majorana modes localized at the hinges between (001) and (100) or (010) surfaces, suggesting that this is a viable platform for observing "higher-order" topological superconductivity. We provide a general theory for these hinge modes and discuss their stability and experimental manifestation. Our work indicates the possible experimental observability of hinge Majorana modes in iron-based topological superconductors.
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We show, theoretically, that a heterostructure of monolayer FeTe_{1-x}Se_{x}-a superconducting quantum spin Hall material-with a monolayer of FeTe-a bicollinear antiferromagnet-realizes a higher order topological superconductor phase characterized by emergent Majorana zero modes pinned to the sample corners. We provide a minimal effective model for this system, analyze the origin of higher order topology, and fully characterize the topological phase diagram. Despite the conventional s-wave pairing, we find a rather surprising emergence of a novel topological nodal superconductor in the phase diagram. Featured by edge-dependent Majorana flat bands, the topological nodal phase is protected by an antiferromagnetic chiral symmetry. We also discuss the experimental feasibility, the estimation of realistic model parameters, and the robustness of the Majorana corner modes against magnetic and potential disorder. Our work provides a new experimentally feasible high-temperature platform for both higher order topology and non-Abelian Majorana physics.
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One of the cornerstones for topological quantum computations is the Majorana zero mode, which has been intensively searched in fractional quantum Hall systems and topological superconductors. Several recent works suggest that such an exotic mode can also exist in a one-dimensional (1D) interacting double-wire setup even without long-range superconductivity. A notable instability in these proposals comes from interchannel single-particle tunneling that spoils the topological ground state degeneracy. Here we show that a 1D Dirac semimetal (DSM) nanowire is an ideal number-conserving platform to realize such Majorana physics. By inserting magnetic flux, a DSM nanowire is driven into a 1D crystalline-symmetry-protected semimetallic phase. Interaction enables the emergence of boundary Majorana zero modes, which is robust as a result of crystalline symmetry protection. We also explore several experimental consequences of Majorana signals.
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In this work, we study the transport through a quantum point contact for bosonic helical liquid that exists at the edge of a bilayer graphene under a strong magnetic field. We identify "smoking gun" transport signatures to distinguish a bosonic symmetry-protected topological (BSPT) state from a fermionic two-channel quantum spin Hall (QSH) state in this system. In particular, a novel charge-insulator-spin-conductor phase is found for the BSPT state, while either the charge-insulator-spin-insulator or the charge-conductor-spin-conductor phase is expected for the two-channel QSH state. Consequently, a simple transport measurement will reveal the fingerprint of bosonic topological physics in bilayer graphene systems.
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Bosonic symmetry protected topological (BSPT) states, the bosonic analogue of topological insulators, have attracted enormous theoretical interest in the last few years. Although BSPT states have been classified by various approaches, there is so far no successful experimental realization of any BSPT state in two or higher dimensions. In this paper, we propose that a two-dimensional BSPT state with U(1)×U(1) symmetry can be realized in bilayer graphene in a magnetic field. Here the two U(1) symmetries represent total spin S^{z} and total charge conservation, respectively. The Coulomb interaction plays a central role in this proposal-it gaps out all the fermions at the boundary, so that only bosonic charge and spin degrees of freedom are gapless and protected at the edge. Based on the above conclusion, we propose that the bulk quantum phase transition between the BSPT and trivial phase, which can be driven by applying both magnetic and electric fields, can become a "bosonic phase transition" with interactions. That is, only bosonic modes close their gap at the transition, which is fundamentally different from all the well-known topological insulator to trivial insulator transitions that occur for free fermion systems. We discuss various experimental consequences of this proposal.
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Although anticancer drug resistance has been linked to high expression of P-glycoprotein and the enhanced DNA repair ability, the biochemical process and the underlying mechanisms of drug resistance are not clear. In order to clarify the biochemical mechanisms of drug resistance during anticancer drug treatment, we studied the metabolomics of MCF-7/S and MCF-7/Adr cell lines, the COC1 and COC1/DDP cell lines, including the metabolic pathways of multidrug-resistant tumor cells and the changes of endogenous substances in cells. The intracellular metabolites were profiled using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In this study, 24 biomarkers in MCF-7/Adr cells and 15 biomarkers in COC1/DDP cells that are involved in some important metabolic pathways were putatively identified. Several metabolic pathways are changed in tumor cells showing drug resistance, such as protein synthesis pathways, cysteine synthesis, the glutamine metabolic pathway, and the ammonia cycle; the first of these are involved in the synthesis of some important proteins including membrane proteins, multidrug resistance-associated proteins, and P-glycoprotein (P-gp). Proteins related to drug resistance were overexpressed in multidrug-resistant tumor cells. These proteins depended on energy and play important roles in the emergence of drug resistance. The changes in glutathione and cysteine metabolic pathways showed that the cells can activate related metabolic pathways and reduce the cell apoptosis when they encounter oxidative damage. These findings indicate that drug resistance is likely associated with increased P-gp synthesis and reduced apoptosis of tumor cells. Graphical Abstract Drug resistance was charactered in the changing of genomics and proteomics. Like enhancing DNA repair, reducing uptake, high P-g protein expression. Here, we studied the changes of metabolite pathway which could be also play an imported role in drug resistance.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Redes e Vias Metabólicas/efeitos dos fármacos , Metabolômica/métodos , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/métodos , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Células MCF-7 , Espectrometria de Massas em Tandem/métodosRESUMO
Cu, Zn-superoxide dismutase (SOD1) is a homodimeric enzyme of approximately 32 kDa. Each monomer contains one Cu(2+) and one Zn(2+) ion, which play catalytic and structural roles in the enzyme. Dimer formation is also essential to its functionality. The spatial structure of this metalloenzyme is also closely related to its bioactivities. Here we investigate the structural and conformational changes of SOD1 in the gas phase by electrospray ionization mass spectrometry (ESI-MS) and ion-mobility (IM) separation combined with tandem mass spectrometry (MS/MS). First, the composition and forms of SOD1 were analyzed by ESI-MS. The dimer, monomer, and apomonomer were observed under different solvent conditions. The dimer was found to be stable, and could retain its native structure in neutral buffer. Ion-mobility separation combined with MS/MS was used to reveal the conformational changes and dissociation process of SOD1 when it was activated in the gas phase. Three different dimeric and two monomeric conformers were observed; three unfolding and dissociation pathways were also identified. The results from this study demonstrate that IM-MS/MS could be used to obtain spatial structural information on SOD1 and that the technique could therefore be employed to investigate the conformational changes in mutant SOD1, which is related to amyotrophic lateral sclerosis and other neurodegenerative disorders.