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1.
J Adv Nurs ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923586

RESUMO

AIMS: In China, more than 30% of patients have not initiated treatment within 30 days of HIV diagnosis. Delayed initiation has a detrimental influence on disease outcomes and increases HIV transmission. The study aims to evaluate the effectiveness of a nurse-led antiretroviral therapy initiation nudging intervention for people newly diagnosed with HIV in China to find the optimal intervention implementation strategy. METHODS: A Hybrid Type II sequential multiple assignment randomized trial will be conducted at four Centers for Disease Control and Prevention in Hunan, China. This study will recruit 447 people newly diagnosed with HIV aged ≥18 years and randomly assign them into two intervention groups and one control group. On top of the regular counselling services and referrals, intervention groups will receive a 4-week, 2-phase intervention based on the dual-system theory and the nudge theory. The control group will follow the currently recommended referral procedures. The primary outcomes are whether treatment is initiated, as well as the length of time it takes. The study outcomes will be measured at the baseline, day 15, day 30, week 12, week 24 and week 48. Generalized estimating equations and survival analysis will be used to compare effectiveness and explore factors associated with antiretroviral therapy initiation. Both qualitative and quantitative information will be collected to assess implementation outcomes. DISCUSSION: Existing strategies mostly target institutional-level factors, with little consideration given to patients' decision-making. To close this gap, we aim to develop an effective theory-driven nudging strategy to improve early ART initiation. IMPACT: This nurse-led study will help to prevent delayed initiation by employing implementation science strategies for people newly diagnosed with HIV. This study contributes to the United Nations' objective of ending the AIDS pandemic by 2030. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070140. The trial was prospectively registered before the first participant was recruited. PATIENT AND PUBLIC INVOLVEMENT: The nudging intervention was finalized through the Nominal Group Technique where we invited five experts in the related field and five people living with HIV to participate.

2.
Nano Lett ; 23(14): 6330-6336, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37440701

RESUMO

Membrane morphology and its dynamic adaptation regulate many cellular functions, which are often mediated by membrane proteins. Advances in DNA nanotechnology have enabled the realization of various protein-inspired structures and functions with precise control at the nanometer level, suggesting a viable tool to artificially engineer membrane morphology. In this work, we demonstrate a DNA origami cross (DOC) structure that can be anchored onto giant unilamellar vesicles (GUVs) and subsequently polymerized into micrometer-scale reconfigurable one-dimensional (1D) chains or two-dimensional (2D) lattices. Such DNA origami-based networks can be switched between left-handed (LH) and right-handed (RH) conformations by DNA fuels and exhibit potent efficacy in remodeling the membrane curvatures of GUVs. This work sheds light on designing hierarchically assembled dynamic DNA systems for the programmable modulation of synthetic cells for useful applications.


Assuntos
Nanoestruturas , Nanoestruturas/química , Conformação de Ácido Nucleico , Nanotecnologia/métodos , DNA/química , Lipossomas Unilamelares , Lipídeos
3.
Int J Mol Sci ; 25(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38203841

RESUMO

The accurate prediction of binding free energy is a major challenge in structure-based drug design. Quantum mechanics (QM)-based approaches show promising potential in predicting ligand-protein binding affinity by accurately describing the behavior and structure of electrons. However, traditional QM calculations face computational limitations, hindering their practical application in drug design. Nevertheless, the fragment molecular orbital (FMO) method has gained widespread application in drug design due to its ability to reduce computational costs and achieve efficient ab initio QM calculations. Although the FMO method has demonstrated its reliability in calculating the gas phase potential energy, the binding of proteins and ligands also involves other contributing energy terms, such as solvent effects, the 'deformation energy' of a ligand's bioactive conformations, and entropy. Particularly in cases involving ionized fragments, the calculation of solvation free energy becomes particularly crucial. We conducted an evaluation of some previously reported implicit solvent methods on the same data set to assess their potential for improving the performance of the FMO method. Herein, we develop a new QM-based binding free energy calculation method called FMOScore, which enhances the performance of the FMO method. The FMOScore method incorporates linear fitting of various terms, including gas-phase potential energy, deformation energy, and solvation free energy. Compared to other widely used traditional prediction methods such as FEP+, MM/PBSA, MM/GBSA, and Autodock vina, FMOScore showed good performance in prediction accuracies. By constructing a retrospective case study, it was observed that incorporating calculations for solvation free energy and deformation energy can further enhance the precision of FMO predictions for binding affinity. Furthermore, using FMOScore-guided lead optimization against Src homology-2-containing protein tyrosine phosphatase 2 (SHP-2), we discovered a novel and potent allosteric SHP-2 inhibitor (compound 8).


Assuntos
Entropia , Ligantes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Solventes
4.
BMC Nurs ; 23(1): 159, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443951

RESUMO

BACKGROUND: The retention of new nurses has become a major challenge for medical institutions. Job embeddedness has been seen as a valuable lens for examining nurse turnover, but greater details about job embeddedness are rarely disclosed, especially among new nurses. This study aimed to reveal how the nursing work environment, head nurse leadership and presenteeism shape job embeddedness in this population from the perspective of conservation of resources (COR) theory. METHOD: A cross-sectional multicentre study involving 436 participants from 10 cities and 33 hospitals was conducted over 4 months. Samples were selected using a two-stage convenience sampling method. A sequential multiple mediation model performed with SPSS-PROCESS was used to analyse the relationships among the nursing work environment, head nurse leadership, presenteeism and job embeddedness. RESULTS: The nursing work environment not only directly affects the job embeddedness of new nurses (ß = 0.480, p < 0.001) but also indirectly affects it through the sequential multiple mediating effects of head nurse leadership and presenteeism (R2 = 0.535, F = 82.160, p < 0.001). CONCLUSIONS: New nurses' job embeddedness needs to be improved. These results suggest that preserving adequate resources for new nurses, such as work environment resources, head nurse leadership resources, and individual productivity resources, is an effective way to shape their job embeddedness. In addition, when a certain resource is insufficient, fully considering the principles of investment and buffering between resources and providing reciprocal, alternative, or buffer resources in a timely manner are necessary to improve new nurses' job embeddedness. LARGE LANGUAGE MODELS: Large language models (LLMs), such as ChatGPT, were not used during the writing of this article. An expert native English speaker performed language revision.

5.
BMC Nurs ; 23(1): 64, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267964

RESUMO

BACKGROUND: Nursing interns often experience lots of challenges during their clinical nursing internships, which can adversely affect career decisions and result in a squandering of nursing education resources. Patient safety attitudes, professional identity and climate of caring may affect nursing interns' clinical experience. However, more evidence is requested to validate these relationships for nursing educators to develop effective education programs and facilitate interns' successful transition. METHODS: This was a cross-sectional study, which used a convenience sampling method to recruit 387 nursing interns during December 2022 to April 2023 in university affiliated hospital in Hunan province, China. Data were collected using standardized scales. Spearman correlation and multiple regression analysis were employed to examine the relationship between transition shock, patient safety attitudes, professional identity, and climate of caring. RESULTS: Nursing interns experienced transition shock at a moderate level and the highest levels of transition shock in response to overwhelming practicum workloads, with the second being related to the conflict between theory and practice. Transition shock was negatively correlated with patient safety attitudes, professional identity and climate of caring among nursing interns. CONCLUSIONS: Nursing managers and educators need to value the transition shock experienced by nursing interns. Our study suggests that developing a strong sense of professional identity and a positive attitude toward patient safety can be effective in reducing the level of transition shock among nursing interns. In addition, a caring climate within the nursing unit can significantly enhance the overall experience of nursing interns. This can be achieved by enhancing the support of clinical mentors, providing patient safety-focused education, and facilitating team communication among nurses.

6.
Org Biomol Chem ; 21(7): 1395-1398, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36688572

RESUMO

Herein, we presented a simple approach for C-H oxidation in the C23 or/and C24 of ursane triterpenoids without any protection of a Δ12,13 double bond. As a result, from commercial ursolic acid (UA), six naturally occurring ursane triterpenoids were synthesized in overall yields of 3.4% to 36.8%, which implied the importance of this approach for the derivation of natural products and their application in biological activity.


Assuntos
Produtos Biológicos , Triterpenos , Triterpenos/farmacologia , Triterpenos/química , Triterpenos Pentacíclicos , Produtos Biológicos/química
7.
Support Care Cancer ; 31(5): 297, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37097532

RESUMO

BACKGROUND: During chemotherapy for multiple myeloma, symptoms include those related to the disease, as well as adverse effects of the treatment. Few studies have explored the relationships between these symptoms. Network analysis could identify the core symptom in the symptom network. OBJECTIVE: The aim of this study was to explore the core symptom in multiple myeloma patients undergoing chemotherapy. METHODS: This was a cross-sectional study in which sequential sampling was used to recruit 177 participants from Hunan, China. Demographic and clinical characteristics were surveyed using a self-developed instrument. The symptoms of chemotherapy-treated multiple myeloma, including pain, fatigue, worry, nausea, and vomiting, were measured using a questionnaire with good reliability and validity. The mean ± SD, frequency, and percentages were used as descriptive statistics. Network analysis was used to estimate the correlation between symptoms. RESULTS: The results showed that 70% of multiple myeloma patients using chemotherapy exhibited pain. In the network analysis, worrying was the dominant symptom, and the strongest relationship was between nausea and vomiting in chemotherapy-treated multiple myeloma patients' symptoms. CONCLUSION: Worrying is the core symptom of multiple myeloma patients. Interventions could be most effective if there is a symptom management focus on worrying when providing care to chemotherapy-treated multiple myeloma patients. Nausea combined with vomiting could be better managed, which would decrease the cost of health care. Understanding the relationship between the symptoms of multiple myeloma patients undergoing chemotherapy is beneficial for precise symptom management. IMPLICATIONS FOR PRACTICE: Nurses and health care teams should be a priority to intervene in the worrying for chemotherapy-treated multiple myeloma patients to maximize the effectiveness of an intervention. Except, nausea and vomiting should be managed together in a clinical setting.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Estudos Transversais , Reprodutibilidade dos Testes , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Dor
8.
Pharmacol Res ; 185: 106477, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36191880

RESUMO

Receptor expression-enhancing proteins (REEPs) are an evolutionarily conserved protein family that is pivotal to the structure and function of the endoplasmic reticulum (ER). The REEP family can be classified into two major subfamilies in higher species, the REEP1-4 and REEP5-6 subfamilies. Within the REEP1-4 subfamily, REEP1 and REEP2 are closely related, and REEP3 and REEP4 are similarly related. The REEP family is widely distributed in various tissues. Recent studies indicate that the REEP family is involved in many pathological and physiological processes, such as ER morphogenesis and remodeling, microtubule cytoskeleton regulation, and the trafficking and expression of G protein-coupled receptors (GPCRs). Moreover, the REEP family plays crucial roles in the occurrence and development of many diseases, including neurological diseases, diabetes, retinal diseases, cardiac diseases, infertility, obesity, oligoarticular juvenile idiopathic arthritis (OJIA), COVID-19, and cancer. In the present review, we describe the distribution and structure of the REEP family. Furthermore, we summarize the functions and the associated diseases of this family. Based on the pleiotropic actions of the REEP family, the study of its family members is crucial to understanding the relevant pathophysiological processes and developing strategies to modulate and control these related diseases.


Assuntos
COVID-19 , Humanos , Retículo Endoplasmático/metabolismo , Proteínas de Transporte/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Citoesqueleto/metabolismo , Proteínas de Membrana Transportadoras/metabolismo
9.
J Nurs Scholarsh ; 54(4): 501-512, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34866319

RESUMO

AIMS: This study aimed to investigate whether the impact of workplace violence (WPV) on nurses' mental health varies with mental resilience and coping strategies. BACKGROUND: Workplace violence is a serious threat to nurses' mental health, and its impact on nurses' mental health is influenced by many factors. METHOD: A cross-sectional study involving 349 participants was conducted over 12 months. The data were analyzed using SPSS 25.0 and SPSS PROCESS macro. RESULTS: In total, 82.52% of nurses were exposed to WPV. WPV not only affects mental health directly but also indirectly through mental resilience. Coping strategies had a moderating effect among WPV, mental resilience and mental health. When nurses coped with psychological violence with intolerance, WPV had a stronger negative effect on their mental health. When nurses coped with psychological violence with tolerance but coped with physical violence with intolerance, mental resilience had a stronger positive effect on their mental health. CONCLUSIONS: Good mental resilience and coping with psychological violence with tolerance while coping with physical violence with intolerance can help buffer WPV and promote mental health. CLINICAL RELEVANCE: Employers who have a "zero tolerance" policy regarding WPV need to re-examine how they currently operate.


Assuntos
Enfermeiras e Enfermeiros , Violência no Trabalho , Adaptação Psicológica , Estudos Transversais , Humanos , Saúde Mental , Inquéritos e Questionários , Local de Trabalho/psicologia , Violência no Trabalho/psicologia
10.
BMC Nurs ; 21(1): 200, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879704

RESUMO

BACKGROUND: Improving the professional identity of nursing intern is significant for enhancing the number of new registered nurses and easing the shortage of nursing personnel. The clinical internship is a key period for the formulation of professional identity. However, we know little about the factors influencing the nursing interns' professional identity during clinical internship. Therefore, this study explore the influencing factors of nursing interns' professional identity during clinical internship. This study will provide evidence and suggestions for generating effective strategies contributing to professional identity improvement of nursing interns. METHODS: This was a cross-sectional study. The convenience sampling was used to recruit 398 nursing interns from a teaching hospital in Hunan, China. The demographic characteristics information was collected by a self-developed questionnaire. The nursing interns' professional identity and potential influencing factors (e.g., work atmosphere, teacher capacity) were measured by questionnaires with good psychometric properties. The appropriate indicators were used for descriptive statistics, and t test, analysis of variance, Pearson's correlation analysis and multiple linear regression were used to analyse the influencing factors. RESULTS: In this study, the influencing factors of nursing interns' professional identity are education level, first choice of major, residential status, work atmosphere, and teacher capacity. The results showed that: (1) the nursing interns with a higher education level reported a lower level of professional identity; (2) the nursing interns whose first choice of major was not nursing discipline reported a lower level of professional identity; (3) the nursing interns live in rural areas (compared to urban areas) reported a higher level of professional identity; (4) the nursing interns in better work atmosphere reported a higher level of professional identity; (5) the nursing interns under the guidance of the teachers equipped with better teaching capacity reported a higher level of professional identity. CONCLUSION: The education level, first choice of major and residential status are influence factors of nursing interns' professional identity. The nursing educators need to pay attention to nursing interns whose first choice is not nursing, and in a bachelor program, who may have a lower level of professional identity. It is crucial to enhance the nursing interns' professional identity by improve the work atmosphere and clinical teachers' capacity, to promote nursing interns to choose nursing as a profession and reduce the shortage of nursing workforce.

11.
Angew Chem Int Ed Engl ; 61(9): e202116324, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-34931420

RESUMO

Inspired by efficient biomolecular reactions in the cell, versatile DNA nanostructures have been explored for manipulating the spatial position and regulating reactions at the molecular level. Spatially controlled arrangement of molecules on the artificial scaffolds generally leads to enhanced reaction activities. Especially, the rich toolset of dynamic DNA nanostructures provides a potential route towards more sophisticated and vigorous regulation of molecular reactions. Herein, a reconfigurable DNA origami domino array (DODA) as a dynamic scaffold was adopted in this work for temporal-controlled and switchable molecular cascade reactions. Dynamic regulation of the assembly of G-quadruplex, hybridization of parallel-stranded duplex and assembly of binary DNAzyme were demonstrated. Molecular cascade reactions on the triggered reconfiguration of DODAs were realized, resulting in more complex, dynamic, and switchable control over the reactions.

12.
J Am Chem Soc ; 142(34): 14566-14573, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32787238

RESUMO

Molecular patterns with nanoscale precision have been used to mimic complex molecular networks. One key challenge in molecular patterns is to perform active pattern operations in controllable systems to fully imitate their complex dynamic behaviors. Here, we present a reconfigurable DNA origami domino array-based dynamic pattern operation (DODA DPO) system to perform proximity-induced molecular control for complex pattern operations. The activatable platform of reconfigurable DODA endows a spontaneous cascade of stacking conformational transformation from the "before" to the "after" conformation by a set of "trigger" DNA strands. The conformational transformation further brings the operational pattern units into close proximity to undergo DNA strand displacement cascades to accomplish three different pattern operations of "writing", "erasing", and "shifting". Our results also demonstrate the reconfigurable DODA DPO system provides a useful basis to study various molecular control analysis in a fully programmable and controllable fashion.


Assuntos
DNA/química , Nanotecnologia , Análise de Sequência com Séries de Oligonucleotídeos , Conformação de Ácido Nucleico
13.
Acta Pharmacol Sin ; 41(6): 791-799, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31937931

RESUMO

Mitochondria serve as sensors of energy regulation and glucose levels, which are impaired by diabetes progression. Catalpol is an iridoid glycoside that exerts a hypoglycemic effect by improving mitochondrial function, but the underlying mechanism has not been fully elucidated. In the current study we explored the effects of catalpol on mitochondrial function in db/db mice and C2C12 myotubes in vitro. After oral administration of catalpol (200 mg·kg-1·d-1) for 8 weeks, db/db mice exhibited a decreased fasting blood glucose level and restored mitochondrial function in skeletal muscle. Catalpol increased mitochondrial biogenesis, evidenced by significant elevations in the number of mitochondria, mitochondrial DNA levels, and the expression of three genes associated with mitochondrial biogenesis: peroxisome proliferator-activated receptor gammaco-activator 1 (PGC-1α), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1). In C2C12 myotubes, catalpol significantly increased glucose uptake and ATP production. These effects depended on activation of AMP-activated protein kinase (AMPK)-mediated mitochondrial biogenesis. Thus, catalpol improves skeletal muscle mitochondrial function by activating AMPK-mediated mitochondrial biogenesis. These findings may guide the development of a new therapeutic approach for type 2 diabetes.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Hipoglicemiantes/uso terapêutico , Glucosídeos Iridoides/farmacologia , Mitocôndrias/efeitos dos fármacos , Administração Oral , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Teste de Tolerância a Glucose , Hipoglicemiantes/metabolismo , Glucosídeos Iridoides/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Relação Estrutura-Atividade
14.
Int J Mol Sci ; 21(13)2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32640753

RESUMO

Photothermal therapy possesses great advantages for the treatment of drug-resistant tumors. Herein, Near Infrared (NIR)-triggered photothermal nanoparticles were developed through loading indocyanine green (ICG), a kind of NIR dye, into amino group-modified silica nanoparticles (SiO2-NH2 NPs). SiO2-NH2 NPs were prepared with immobilization of the amino groups into the framework of silica nanoparticles (SiO2 NPs) by employing (3-aminopropyl)-triethoxysilane (APTES). Before and after the modification of the amino group, the particle sizes of SiO2 NPs showed similar value, around 100 nm. ICG was further adsorbed into SiO2-NH2 NPs by electrostatic attraction to enable SiO2-NH2@ICG NPs as a kind of photothermal agent. The loading rate of ICG to SiO2-NH2 was greatly increased compared to unmodified SiO2, and the stability of ICG was also improved. Moreover, the SiO2-NH2@ICG NPs exhibited efficient photothermal effects due to ICG transforming laser power into local heat through the connected ICG, when NIR laser irradiation turned on for a couple of minutes. Finally, the in vitro antitumor efficacy of SiO2-NH2@ICG NPs was investigated by recording cell proliferation rate and further chronicled the apoptotic morphology evidence by a Calcein-AM/PI fluorescent staining assay, indicating the efficient photothermal targeted therapy for the HepG2 tumor cells.


Assuntos
Hipertermia Induzida/métodos , Verde de Indocianina/química , Neoplasias Hepáticas/terapia , Nanopartículas/administração & dosagem , Terapia Fototérmica/métodos , Dióxido de Silício/química , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Neoplasias Hepáticas/metabolismo , Nanopartículas/química
15.
Angew Chem Int Ed Engl ; 59(31): 12991-12997, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32304157

RESUMO

DNA nanostructures with programmable nanoscale patterns has been achieved in the past decades, and molecular information coding (MIC) on those designed nanostructures has gained increasing attention for information security. However, achieving steganography and cryptography synchronously on DNA nanostructures remains a challenge. Herein, we demonstrated MIC in a reconfigurable DNA origami domino array (DODA), which can reconfigure intrinsic patterns but keep the DODA outline the same for steganography. When a set of keys (DNA strands) are added, the cryptographic data can be translated into visible patterns within DODA. More complex cryptography with the ASCII code within a programmable 6×6 lattice is demonstrated to demosntrate the versatility of MIC in the DODA. Furthermore, an anti-counterfeiting approach based on conformational transformation-mediated toehold strand displacement reaction is designed to protect MIC from decoding and falsification.

16.
Angew Chem Int Ed Engl ; 59(51): 23277-23282, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-32894584

RESUMO

DNA origami enables the manipulation of objects at nanoscale, and demonstrates unprecedented versatility for fabricating both static and dynamic nanostructures. In this work, we introduce a new strategy for transferring modular reconfigurable DNA nanostructures from two-dimensional to three-dimensional. A 2D DNA sheet could be modularized into connected parts (e.g., two, three, and four parts in this work), which can be independently transformed between two conformations with a few DNA "trigger" strands. More interestingly, the transformation of the connected 2D modules can lead to the controlled, resettable structural conversion of a 2D sheet to a 3D architecture, due to the constraints induced by the connections between the 2D modules. This new approach can provide an efficient mean for constructing programmable, higher-order, and complex DNA objects, as well as sophisticated dynamic substrates for various applications.

17.
J Cell Physiol ; 234(5): 7510-7523, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30362548

RESUMO

Pre-diabetes is characterized by impaired glucose tolerance (IGT) and/or impaired fasting glucose. Impairment of skeletal muscle function is closely associated with the progression of diabetes. However, the entire pathological characteristics and mechanisms of pre-diabetes in skeletal muscle remain fully unknown. Here, we established a mouse model of pre-diabetes, in which 6-week-old male C57BL6/J mice were fed either normal diet or high-fat diet (HFD) for 8 or 16 weeks. Both non-fasting and fasting glucose levels and the results of glucose and insulin tolerance tests showed that mice fed an 8-week HFD developed pre-diabetes with IGT; whereas mice fed a 16-week HFD presented with impaired fasting glucose and impaired glucose tolerance (IFG-IGT). Mice at both stages of pre-diabetes displayed decreased numbers of mitochondria in skeletal muscle. Moreover, IFG-IGT mice exhibited decreased mitochondrial membrane potential and ATP production in skeletal muscle and muscle degeneration characterized by a shift in muscle fibers from predominantly oxidative type I to glycolytic type II. Western blotting and histological analysis confirmed that myoblast differentiation was only inhibited in IFG-IGT mice. For primary skeletal muscle satellite cells, inhibition of differentiation was observed in palmitic acid-induced insulin resistance model. Moreover, enhanced myoblast differentiation increased glucose uptake and insulin sensitivity. These findings indicate that pre-diabetes result in mitochondrial dysfunction and inhibition of myoblast differentiation in skeletal muscle. Therefore, interventions that enhance myoblast differentiation may improve insulin resistance of diabetes at the earlier stage.


Assuntos
Diferenciação Celular/fisiologia , Dieta Hiperlipídica/efeitos adversos , Mitocôndrias/fisiologia , Doenças Mitocondriais/fisiopatologia , Mioblastos/fisiologia , Estado Pré-Diabético/fisiopatologia , Trifosfato de Adenosina/metabolismo , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Glicemia/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Jejum/metabolismo , Jejum/fisiologia , Glucose/metabolismo , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Resistência à Insulina/fisiologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Ácido Palmítico/farmacologia , Estado Pré-Diabético/metabolismo , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Células Satélites de Músculo Esquelético/metabolismo , Células Satélites de Músculo Esquelético/patologia
18.
Small ; 15(26): e1805554, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31018040

RESUMO

Structural deoxyribonucleic acid (DNA) nanotechnology offers a robust platform for diverse nanoscale shapes that can be used in various applications. Among a wide variety of DNA assembly strategies, DNA origami is the most robust one in constructing custom nanoshapes and exquisite patterns. In this account, the static structural and functional patterns assembled on DNA origami are reviewed, as well as the reconfigurable assembled architectures regulated through dynamic DNA nanotechnology. The fast progress of dynamic DNA origami nanotechnology facilitates the construction of reconfigurable patterns, which can further be used in many applications such as optical/plasmonic sensors, nanophotonic devices, and nanorobotics for numerous different tasks.


Assuntos
DNA/química , Nanoestruturas/química , Nanotecnologia/métodos
19.
Toxicol Appl Pharmacol ; 362: 150-158, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30419252

RESUMO

8-methoxypsoralen (8-MOP) with ultraviolet A radiation therapy (PUVA) is the standard therapy for patients with psoriasis, despite the reported potential risks of 8-MOP-induced cholestatic liver injury in both humans and animals. Usually, patients with chronic cholestasis exhibit lower serum 25-hydroxy vitamin D (25(OH)D) levels. But those patients receiving PUVA for psoriasis showed an increase in serum 25(OH)D levels, probably highlighting that the vitamin D-vitamin D nuclear receptor (VD-VDR) axis play a protective role in 8-MOP-induced hepatotoxicity. The present study confirmed 8-MOP could increase serum 25(OH)D levels in conventional lighting and diet (CLD) and vitamin D deficient (VDD) Sprague-Dawley rats. Potential liver risks were also found in CLD and VDD rats after 8-MOP treatment. We proved that 8-MOP could be a potent ligand for VDR using molecular docking and luciferase report assay. Effect of 8-MOP on VDR subcellular distribution was determined using human liver cell line L02. We found 8-MOP could increase VDR protein expression in the nuclear and cytosol extracts and also total cell extracts in L02. siRNAs for VDR were used to determine the role of VDR in protecting 8-MOP-induced cholestasis and potential cellular mechanisms. The results showed 8-MOP could affect the CYP7A1, SHP and MRP3 expression via VDR, and such effects could be reversed by knockdown of VDR expression, suggesting a vital role of VDR involved in 8-MOP-regulated bile acid synthesis and transportation. In conclusion, these results revealed activation of VD-VDR axis may play a beneficial role in 8-MOP-mediated regulation of bile acid synthesis and transportation.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Metoxaleno/toxicidade , Fármacos Fotossensibilizantes/toxicidade , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , Animais , Linhagem Celular , Feminino , Homeostase , Humanos , Fígado/efeitos dos fármacos , Modelos Moleculares , Ratos Sprague-Dawley , Receptores de Calcitriol/genética , Deficiência de Vitamina D/metabolismo
20.
Bioinformatics ; 32(18): 2863-5, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27153663

RESUMO

MOTIVATION: Many biochemical systems require stochastic descriptions. Unfortunately these can only be solved for the simplest cases and their direct simulation can become prohibitively expensive, precluding thorough analysis. As an alternative, moment closure approximation methods generate equations for the time-evolution of the system's moments and apply a closure ansatz to obtain a closed set of differential equations; that can become the basis for the deterministic analysis of the moments of the outputs of stochastic systems. RESULTS: We present a free, user-friendly tool implementing an efficient moment expansion approximation with parametric closures that integrates well with the IPython interactive environment. Our package enables the analysis of complex stochastic systems without any constraints on the number of species and moments studied and the type of rate laws in the system. In addition to the approximation method our package provides numerous tools to help non-expert users in stochastic analysis. AVAILABILITY AND IMPLEMENTATION: https://github.com/theosysbio/means CONTACTS: m.stumpf@imperial.ac.uk or e.lakatos13@imperial.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Software , Processos Estocásticos , Simulação por Computador , Expressão Gênica , Cinética , Modelos Estatísticos
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