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OBJECTIVE: this retrospective study aims to compare the prevalence and diagnostic agreement of sarcopenic obesity (SO) using different obesity diagnostic methods among Chinese community-dwelling older adults. METHODS: SO was diagnosed with sarcopenia and obesity diagnostic methods. Sarcopenia was defined using the Asian Working Group for Sarcopenia criteria 2019 (AWGS2019). Four widely used indicators were used to define obesity: body mass index (BMI), waist circumference (WC), percent of body fat (PBF) and visceral fat area (VFA). Cohen's kappa was used to analyse the diagnosis agreement of SO between different diagnostic methods. RESULTS: a total of 1,050 participants were included, including 347 men (71.3 ± 7.4 years) and 703 women (69.9 ± 7.5 years). The prevalence of sarcopenia was 25% in total participants, there was no difference between men (24.2%) and women (25.5%), (P = 0.705). With different obesity diagnostic methods, the obesity prevalence ranged from 4.1 to 42.2%, the SO prevalence was 0.1-7.9%. The diagnosis agreement of SO was poor-to-moderate (κ ranged from -0.002 to 0.682). Among the four diagnostic methods, AWGS combined with BMI had the poorest agreement (κ = -0.002 with other methods), AWGS combined with VFA had the best agreement (κ = 0.641 and 0.682 with AWGS combined with PBF and with AWGS combined with WC, respectively). CONCLUSION: the prevalence of SO vary considerably and the diagnostic agreement is poor-to-moderate with non-uniform diagnostic methods. BMI has the lowest sensitivity, whereas VFA has the highest sensitivity in diagnosis of SO, and VFA has a relatively good diagnostic agreement with other diagnostic methods.
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Sarcopenia , Idoso , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Vida Independente , Masculino , Obesidade/diagnóstico , Obesidade/epidemiologia , Prevalência , Estudos Retrospectivos , Sarcopenia/diagnóstico , Sarcopenia/epidemiologiaRESUMO
Using high pressure homogenization method combined with spray-drying, budesonide-loaded chitosan microparticles were prepared and the in vitro release profile was investigated. The microparticles were then blended with lactose using a vortex mixer, influence of mixing speed, mixing time on drug recovery rate and content homogeneity were investigated. Meanwhile, influence of lactose content on drug recovery rate, content homogeneity, powder flowability and in vitro deposition were studied. It turned out that budesonide was released from the microparicles in a sustained manner, with fine particle fraction as high as 46.0%, but the powder flowability was poor. After blending with 10 times of lactose, the drug recovery rate was 96.5%, with relative standard deviation of drug content 2.5%, and fine particle fraction of the formulation increased to 59.6% with good flowability. It's demonstrated that using a vortex mixer, budesonide sustained-release dry powder for inhalation with good recovery and content homogeneity could be prepared, the formulation had good flowability and was suitable for pulmonary inhaling.
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Budesonida/química , Lactose/química , Pós , Administração por Inalação , Química Farmacêutica , Quitosana , Preparações de Ação Retardada/química , Portadores de Fármacos , Tamanho da PartículaRESUMO
A series of novel benzo[b][1,4]oxazin-3(4H)-one derivatives were synthesized as platelet aggregation inhibitors for structure-activity relationships (SAR) analysis. The synthetic pattern, involved Smiles rearrangement for the preparation of benzoxazine, was proven to be more efficient than the conventional methods. Biological evaluation demonstrated that among all the synthesized compounds, compound 9u (IC50=9.20µM) exhibited the most potent inhibition activity compared with aspirin, the positive control (IC50=7.07µM). Molecular docking revealed that these set of compounds could be the GPIIb/IIIa antagonist for that they could be situated in the binding site of GPIIb/IIIa receptor quite well.
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Benzoxazinas/química , Piperazinas/síntese química , Inibidores da Agregação Plaquetária/síntese química , Benzoxazinas/síntese química , Benzoxazinas/metabolismo , Sítios de Ligação , Domínio Catalítico , Simulação de Acoplamento Molecular , Piperazinas/química , Piperazinas/metabolismo , Inibidores da Agregação Plaquetária/química , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: Handgrip strength and the 5-time chair-stand test are the two important muscle strength measures run through the whole sarcopenia diagnosis algorithm. There is a lack of evidence to confirm which muscle strength measures have a higher detection rate of sarcopenia among Chinese older adults, which is a challenge for community workers to choose the muscle strength measures and to identify more sarcopenia in clinical practice. OBJECTIVE: We aimed to investigate the prevalence and diagnostic agreement of sarcopenia based on handgrip strength and the 5-time chair-stand test among Chinese community-dwelling older adults. METHODS: This cross-sectional study sampled 1027 community-dwelling older adults from Hunan, China. We used handgrip strength and the 5-time chair-stand test to assess participants' muscle strength and used gait speed and bioimpedance analysis (BIA) to assess physical performance and skeletal muscle mass, respectively. The kappa values of the agreement test were used to evaluate the agreement of handgrip strength and 5-time chair-stand tests in the assessment of sarcopenia. RESULTS: A total of 1027 participants were included in this analysis including 337 males and 690 females with an average age of 70.35 ± 7.24 years. The prevalence of possible sarcopenia, confirmed sarcopenia and severe sarcopenia based on handgrip strength was 50.8%, 20.3% and 14.5% respectively, while the corresponding prevalence for using the 5-time chair-stand test was 27.6%, 10.8% and 10.9%. The kappa value of the consistency test between handgrip strength and 5-time chair-stand test in the assessment of possible sarcopenia, confirmed and severe sarcopenia was 0.26, 0.51 and 0.62, respectively (p < 0.001 for all). CONCLUSIONS: The prevalence of possible sarcopenia, confirmed sarcopenia and severe sarcopenia based on handgrip strength was significantly higher than that of the 5-time chair-stand test. We recommend handgrip strength as the preferred method of muscle strength measurement for Chinese community-dwelling older adults and use 5-time chair-stand tests when handgrip strength is not available. IMPLICATIONS FOR PRACTICE: The findings provide information and suggestions to healthcare providers for choosing the muscle strength measures to detect more sarcopenia in clinical practice. Compared with the 5-time chair-stand test, handgrip strength has a better performance to identify sarcopenia in Chinese community-dwelling older adults.
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Avaliação Geriátrica , Força da Mão , Vida Independente , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Masculino , Força da Mão/fisiologia , Feminino , Idoso , Estudos Transversais , Prevalência , China/epidemiologia , Avaliação Geriátrica/métodos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , População do Leste AsiáticoRESUMO
BACKGROUND: The five-time chair stand test (5CST) as an indicator of muscle strength and physical function is the first step in assessing sarcopenia. We aimed to determine the optimal cut-off value of the 5CST for assessing older adults with sarcopenia in the Chinese community. METHODS: We used a stratified cluster random sampling method to recruit older adults from Chinese communities. The handgrip strength was assessed using an electronic handgrip dynamometer. The 5CST and gait speed were assessed by the trained researchers. The bioimpedance analysis device was used to evaluate the skeletal muscle index. We used the Asian Working Group for Sarcopenia diagnosis criteria as the gold standard. According to the receiver operating characteristic curve, we determine the optimal cut-off value using the Youden index. RESULTS: A total of 1027 participants were included in this analysis, including 337 men and 690 women with an average age of 70.35 ± 7.24 years. The prevalence of sarcopenia in total participants was 24.9%. The optimal cut-off value of 5CST in the total population was 10.9 s. Stratified by age and gender, for the older adults aged 60-69 years, the optimal cut-off values were 9.2 s in men and 10.8 s in women; for the older adults aged 70-79 years, cut-off values were 10.2 s in men and 10.9 s in women; and for the older adults over 80 years, cut-off values were 14.0 s in men and 11.5 s in women (all P < 0.001). The areas under the curve of 5CST were 0.632 in men and 0.650 in women (both P < 0.001). Using the newly defined cut-off values, the prevalence of sarcopenia increased significantly (P < 0.001). CONCLUSIONS: We determined the optimal cut-off value of the 5CST for assessing older adults with sarcopenia in the Chinese community, and this cut-off can significantly improve the detection rate of sarcopenia. The cut-off determined in our study will help community workers detect more people with sarcopenia and benefit from early intervention and management of sarcopenia in practice.
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Sarcopenia , Masculino , Idoso , Humanos , Feminino , Pessoa de Meia-Idade , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Vida Independente , Força da Mão , Avaliação Geriátrica/métodos , China/epidemiologiaRESUMO
BACKGROUND: The implementation of the rotation system in the Chinese medical industry has achieved significant results. OBJECTIVES: The present study aims to 1) explore the strengths, weaknesses, opportunities and challenges of rotational nursing department implementation and 2) provide references for developing nursing staff's competencies in leadership, performance evaluation, quality of care, communication in relationships and human resources. METHODS: A total of 16 rotational nursing department staff members from a tertiary tuberculosis specialist hospital in Beijing were interviewed, and the interview data were analysed using a strengths, weaknesses, opportunities and threats analysis and class analysis. RESULTS: The advantages of the rotational nursing department included: (1) stimulating the nursing staff's enthusiasm and creativity; (2) strengthening the communication and collaboration between departments; (3) improving the detailed management of nursing quality; and (4) enhancing the nursing staff's comprehensive abilities. The disadvantages included: (1) the design of the rotation programme focusing on practice; (2) a lack of personalisation; and (3) imperfect performance assessment of the rotating staff. Opportunities included: (1) deepening the connotation of nursing job management and (2) developing the construction of nursing discipline and the need for personal career development and value realisation. Threats included the lack of a sound rotation management model to draw on. CONCLUSION: A rotational nursing department is conducive to enhancing the competence of nursing staff in management positions and providing new ideas for hospitals to select and train nursing management talents. By taking full advantage of the benefits of vertical nursing management, designing personalised rotation training programmes, building a diversified learning and training platform and developing a positive performance incentive mechanism is recommended to fully engage the role of rotation in nursing management talent training.
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Recursos Humanos de Enfermagem Hospitalar , Humanos , Recursos Humanos de Enfermagem Hospitalar/educação , Liderança , Competência Clínica , China , Feminino , Qualidade da Assistência à Saúde , MasculinoRESUMO
CONTEXT: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation in the synovial membrane of affected joints. It has been shown that several kinds of cytokine were increased in synovial fluid, while the underlying mechanism remains poorly understood. OBJECTIVES: NF-κB activator 1 (Act1) is a recently identified protein binding to the IκB kinase complex. Our study aimed to investigate the expression of Act1 induced by cytokine IL-17 stimulation in SW982 cells. MATERIALS AND METHODS: The human synovial sarcoma cell line SW982 and primary cultured RA fibroblast-like synovial cells were used. RT-PCR and Western blot assays were selected to investigate the genetic and protein expression of Act1. Additionally, four independent Act1 small interfering RNA (siRNA) oligonucleotides were designed and obtained according to the GenBank cDNA, the sequence of Act1 (Traf3ip2). Finally, enzyme-linked immunosorbent assay (ELISA) double antibody sandwich was used to assay supernatant IL-6 and IL-8 concentrations. RESULTS: The Act1 mRNA expression level increased significantly after stimulation with IL-17 (5-100 ng/ml) in SW982 cells. Additionally, the level of Act1 mRNA expression correlated positively with the concentration of IL-17 (p < 0.01). IL-17 induced IL-6 and IL-8 in SW982 cells was in a concentration- and time-dependent way. Furthermore, ELISA assay revealed that IL-17 (20 ng/ml) significantly increased IL-6 (1927.4 ± 288.77 versus 786.5 ± 172.42 ng/ml, p < 0.01) and IL-8 levels (984.8 ± 95.09 ng/ml versus 307.1 ± 90.83 ng/ml, p < 0.01) compared with control group after stimulation for 24 h. However, transfection of Traf3ip2 siRNA markedly decreased IL-6 (995.9 ± 115.30 ng/ml versus 1816.1 ± 273.27 ng/ml, p < 0.01) and IL-8 levels (575.6 ± 65.96 ng/ml versus 929.4 ± 124.39 ng/ml, p < 0.01) compared to transfection negative control. These findings suggested that IL-6 and IL-8 level induced by IL-17 in SW982 cells could be reversed by down-regulation of Act1 expression level with Traf3ip2 siRNA. CONCLUSION: Our results suggested that Act1 might play a key role in the pathophysiology and the treatment of RA.
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Interleucina-17/farmacologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Membrana Sinovial/efeitos dos fármacos , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Interferência de RNA , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/metabolismo , Fatores de Tempo , Transfecção , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/genética , Regulação para CimaRESUMO
INTRODUCTION: The objective of this study was to investigate the willingness of patients with tuberculosis (TB) to use mobile medical services (mHealth) and its influencing factors, so as to provide theoretical guidance for optimizing the TB mobile medical platform and improve the willingness of patients to use mHealth. METHODOLOGY: In this cross-sectional study, convenience sampling method was used to investigate patients with TB from the outpatient clinics of two TB specialized hospitals (Beijing Thoracic Tumor and Tuberculosis Hospital and Tuberculosis Prevention and Treatment Hospital of Shaanxi Province) from January to June 2021 using a self-designed questionnaire. RESULTS: Out of 231 patients, only 90 (38.96%) were aware of mHealth services, and 63 (27.27%) had used mHealth services. Among the 63 patients who had used mHealth services, the proportion of mobile medical forms based on WeChat platform was 74.89%. Patients' willingness to use mHealth was scored (11.49 ± 2.53). Univariate analysis showed that the scores of patients' willingness to use mHealth differed by gender and the different ways of affording healthcare (p < 0.05). Regression analysis showed that the influencing factors of willingness to use mHealth in patients with TB included attitude towards use (0.750), health beliefs (0.091) and social impact (0.169) (adjusted R2 = 0.781, p < 0.001). CONCLUSIONS: Patients' awareness of the advantages of the new medical model needs to be improved. Optimized design can improve the willingness of patients to use mHealth services and improve the role of mHealth in patient management.
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Telemedicina , Tuberculose , Humanos , Estudos Transversais , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controle , Instituições de Assistência Ambulatorial , Inquéritos e QuestionáriosRESUMO
The origin of domesticated Asian rice (Oryza sativa L.) has been controversial for more than half a century. The debates have focused on two leading hypotheses: a single domestication event in China or multiple domestication events in geographically separate areas. These two hypotheses differ in their predicted history of genes/alleles selected during domestication. Here we amassed a dataset of 1,578 resequenced genomes, including an expanded sample of wild rice from throughout its geographic range. We identified 993 selected genes that generated phylogenetic trees on which japonica and indica formed a monophyletic group, suggesting that the domestication alleles of these genes originated only once in either japonica or indica. Importantly, the domestication alleles of most selected genes (~80%) stemmed from wild rice in China, but the domestication alleles of a substantial minority of selected genes (~20%) originated from wild rice in South and Southeast Asia, demonstrating separate domestication events of Asian rice.
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Domesticação , Oryza , Filogenia , Oryza/genética , China , AlelosRESUMO
Vibrio anguillarum is part of the natural flora in the aquatic habitat, but under certain circumstances it can cause terminal hemorrhagic septicemia in marine fish due to the action of virulence-associated proteins. In our study, V. anguillarum MN and 3010 were identified as serotype O1 by AFLP analysis, and the virulence of V. anguillarum MN was shown 50-fold higher than that of the strain 3101 by LD(50) tests with Japanese flounder Paralichthys olivaceus. Nine spots were noted as differentially expressed proteins by comparing the cellular and extracellular protein profiles of V. anguillarum MN and 3101. Mass spectrometry results showed OmpU and PrtV were highly expressed in the virulent strain MN but lowly expressed in the less virulent strain 3101. Expression level confirmed by semiquantitative RT-PCR showed that ompU and prtV were indeed highly expressed in the virulent strain MN. Together with similar amino acid sequences of both OmpU and PrtV in V. anguillarum MN and 3101, our study indicated that the expression level of OmpU and PrtV may be associated with the virulence of V. anguillarum.
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Proteômica/métodos , Vibrio/metabolismo , Vibrio/patogenicidade , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Análise por Conglomerados , Eletroforese em Gel Bidimensional , Espaço Extracelular/química , Espaço Extracelular/metabolismo , Espaço Intracelular/química , Espaço Intracelular/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Filogenia , RNA Mensageiro/análise , Alinhamento de Sequência , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Vibrio/classificação , Vibrio/genética , VirulênciaRESUMO
A drug carrier based on glycyrrhetinic acid-modified sulfated chitosan (GA-SCTS) was synthesized. The glycyrrhetinic acid (GA) acted as both a hydrophobic group and a liver-targeting ligand. The GA-SCTS micelles displayed rapid and significant ability to target the liver in vivo. The IC(50) for doxorubicin (DOX)-loaded GA-SCTS micelles (DOX/SA-SCTS micelles) against HepG2 cells was 54.7 ng/mL, which was extremely lower than the amount of no-GA-modified DOX-loaded micelles. In addition, DOX/SA-SCTS micelles could target specifically the liver cancer cells. They had higher affinity for the liver cancer cells (HepG2 cells) than for the normal liver cells (Chang liver cells). There was nearly 2.18-fold improvement in uptake of the DOX/SA-SCTS micelles by HepG2 cells than that by Chang liver cells. These results indicate that GA-SCTS is not only an excellent carrier for drugs, but also a potential vehicle for liver-cancer targeting.
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Quitosana/química , Doxorrubicina/farmacocinética , Ácido Glicirretínico/química , Fígado/química , Fígado/metabolismo , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Animais , Cristalização/métodos , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Células Hep G2 , Humanos , Camundongos , Sulfatos/químicaRESUMO
Four types of doxorubicin (DOX)-loaded polymeric micelles based on hydrophobically-modified sulfated chitosan (SCTS) were prepared. The hydrophobic group was composed of glycyrrhetinic acid (GA), cholic acid, stearic acid (SA) or lauric aldehyde. DOX encapsulation depended on several parameters, including the degree of substitution of the sulfate group and the hydrophobic group, and the type of hydrophobic group. Of these micelles, GA-SCTS micelles had the best capability to solubilize DOX. In addition, GA-SCTS micelles had the ability to target HepG(2) cells, and the IC50 for DOX-loaded GA-SCTS micelles was 54.7 ng/mL, which was much lower than that of the other micelles. Further studies on the DOX-loaded GA-SCTS micelles showed that they were stable in salt and protein solutions, in cell culture media, and during long-term storage (6 months). Based on these results, these micelles may be a promising DOX-encapsulated formulation, particularly, GA-SCTS as a potential vehicle for liver-targeted delivery.
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Antineoplásicos/administração & dosagem , Quitosana/química , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Micelas , Polímeros , Sulfatos/química , Linhagem Celular , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Tamanho da PartículaRESUMO
OBJECTIVE: To establish and validate a nomogram that predicts the risk of sarcopenia for community-dwelling older residents. DESIGN: Retrospective study. SETTING AND PARTICIPANTS: A total of 1050 community-dwelling older adults. METHODS: Data from a survey of community-dwelling older residents (≥60 years old) in Hunan, China, from June to September 2019 were retrospectively analyzed. The survey included general demographic information, diet, and exercise habits. Sarcopenia diagnosis was according to 2019 Asian Working Group for Sarcopenia criteria. Participants were randomly divided into the development group and validation groups. Independent risk factors were screened by multivariate logistic regression analysis. Based on the independent risk factors, a nomogram model was developed to predict the risk of sarcopenia for community-dwelling older adults. Both in the development and validation sets, the discrimination, calibration, and clinical practicability of the nomogram were verified using receiver operating characteristic curve analysis, Hosmer-Lemeshow test, and decision curve analysis, respectively. RESULTS: Sarcopenia was identified in 263 (25.0%) participants. Age, body mass index, marital status, regular physical activity habit, uninterrupted sedentary time, and dietary diversity score were significant contributors to sarcopenia risk. A nomogram for predicting sarcopenia in community-dwelling older adults was developed using these factors. Receiver operating characteristic curve analysis showed that the area under the curve was 0.827 (95% CI 0.792-0.860) and 0.755 (95% CI 0.680-0.837) in the development and validation sets, respectively. The Hosmer-Lemeshow test yielded P values of .609 and .565, respectively, for the 2 sets. The nomogram demonstrated a high net benefit in the clinical decision curve in both sets. CONCLUSIONS AND IMPLICATIONS: This study developed and validated a risk prediction nomogram for sarcopenia among community-dwelling older adults. Sarcopenia risk was classified as low (<11%), moderate (11%-70%), and high (>70%). This nomogram provides an accurate visual tool to medical staff, caregivers, and older adults for prediction, early intervention, and graded management of sarcopenia.
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Sarcopenia , Idoso , Humanos , Vida Independente , Pessoa de Meia-Idade , Nomogramas , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/diagnósticoRESUMO
BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a pleiotropic monocarboxypeptidase capable of metabolizing several peptide substrates. We hypothesized that ACE2 is a negative regulator of angiotensin II (Ang II)-mediated signaling and its adverse effects on the cardiovascular system. METHODS AND RESULTS: Ang II infusion (1.5 mg x kg(-1) x d(-1)) for 14 days resulted in worsening cardiac fibrosis and pathological hypertrophy in ACE2 knockout (Ace2(-/y)) mice compared with wild-type (WT) mice. Daily treatment of Ang II-infused wild-type mice with recombinant human ACE2 (rhACE2; 2 mg x kg(-1) x d(-1) IP) blunted the hypertrophic response and expression of hypertrophy markers and reduced Ang II-induced superoxide production. Ang II-mediated myocardial fibrosis and expression of procollagen type I alpha 1, procollagen type III alpha 1, transforming growth factor-beta1, and fibronectin were also suppressed by rhACE2. Ang II-induced diastolic dysfunction was inhibited by rhACE2 in association with reduced plasma and myocardial Ang II and increased plasma Ang 1-7 levels. rhACE2 treatment inhibited Ang II-mediated activation of protein kinase C-alpha and protein kinase C-beta1 protein levels and phosphorylation of the extracellular signal-regulated 1/2, Janus kinase 2, and signal transducer and activator of transcription 3 signaling pathways in wild-type mice. A subpressor dose of Ang II (0.15 mg . kg(-1) . d(-1)) resulted in a milder phenotype that was strikingly attenuated by rhACE2 (2 mg x kg(-1) x d(-1) IP). In adult ventricular cardiomyocytes and cardiofibroblasts, Ang II-mediated superoxide generation, collagen production, and extracellular signal-regulated 1/2 signaling were inhibited by rhACE2 in an Ang 1-7-dependent manner. Importantly, rhACE2 partially prevented the development of dilated cardiomyopathy in pressure-overloaded wild-type mice. CONCLUSIONS: Elevated Ang II induced hypertension, myocardial hypertrophy, fibrosis, and diastolic dysfunction, which were exacerbated by ACE2 deficiency, whereas rhACE2 attenuated Ang II- and pressure-overload-induced adverse myocardial remodeling. Hence, ACE2 is an important negative regulator of Ang II-induced heart disease and suppresses adverse myocardial remodeling.
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Cardiomegalia/enzimologia , Cardiomegalia/prevenção & controle , Regulação para Baixo/fisiologia , Hipertrofia Ventricular Esquerda/enzimologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Miocárdio/enzimologia , Miocárdio/patologia , Peptidil Dipeptidase A/deficiência , Angiotensina II/administração & dosagem , Angiotensina II/antagonistas & inibidores , Angiotensina II/biossíntese , Enzima de Conversão de Angiotensina 2 , Animais , Células CHO , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Células Cultivadas , Cadeia alfa 1 do Colágeno Tipo I , Cricetinae , Cricetulus , Fibrose , Humanos , Hipertrofia Ventricular Esquerda/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peptidil Dipeptidase A/administração & dosagem , Peptidil Dipeptidase A/fisiologia , Proteínas Recombinantes/administração & dosagemRESUMO
Recently, many efforts have been devoted to investigating the application of functionalized micelles as targeted drug delivery carriers. In this study, glycyrrhetinic acid (GA, a liver targeting ligand) modified poly(ethylene glycol)-b-poly(γ-benzyl L-glutamate) micelles were prepared and evaluated as a potential liver-targeted drug carrier. The aggregation behavior, stability, size and morphology of the micelles were investigated. Anticancer drug doxorubicin (DOX) was encapsulated in the micelles. The drug release profile, in vivo distribution and the cytotoxicity against hepatic carcinoma QGY-7703 cells of DOX-loaded micelles were studied. The results indicated that the release profile was pH-dependent with Fickian diffusion kinetics. The micelles were remarkably targeted to the liver, inducing a 4.9-fold higher DOX concentration than that for free DOX · HCl. The DOX-loaded micelles exhibited almost twofold more potent cytotoxicity compared with DOX · HCl, and the cytotoxicity was time- and dosage-dependent. These results suggest that GA-functionalized micelles represent a promising carrier for drug delivery to the liver.
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Portadores de Fármacos/química , Ácido Glicirretínico/química , Fígado/metabolismo , Micelas , Animais , Antineoplásicos/administração & dosagem , Biodegradação Ambiental , Sistemas de Liberação de Medicamentos , Hepatócitos/metabolismo , Ligantes , Modelos Químicos , Polietilenoglicóis/química , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/química , Polímeros/química , RatosRESUMO
Sarcopenia is a progressive and widespread skeletal muscle disease that is related to an increased possibility of adverse consequences such as falls, fractures, physical disabilities and death, and its risk increases with age. With the deepening of the understanding of sarcopenia, the disease has become a major clinical disease of the elderly and a key challenge of healthy ageing. However, the exact molecular mechanism of this disease is still unclear, and the selection of treatment strategies and the evaluation of its effect are not the same. Most importantly, the early symptoms of this disease are not obvious and are easy to ignore. In addition, the clinical manifestations of each patient are not exactly the same, which makes it difficult to effectively study the progression of sarcopenia. Therefore, it is necessary to develop and use animal models to understand the pathophysiology of sarcopenia and develop therapeutic strategies. This paper reviews the mouse models that can be used in the study of sarcopenia, including ageing models, genetically engineered models, hindlimb suspension models, chemical induction models, denervation models, and immobilization models; analyses their advantages and disadvantages and application scope; and finally summarizes the evaluation of sarcopenia in mouse models.
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Envelhecimento Saudável , Sarcopenia , Idoso , Envelhecimento , Animais , Elevação dos Membros Posteriores , Humanos , Camundongos , Músculo Esquelético/patologia , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Sarcopenia/patologiaRESUMO
Sarcopenia is a common geriatric disorder characterized by decreased muscle strength, low muscle mass and poor physical performance. This aging-related skeletal muscle deterioration leads to adverse outcomes and severely impairs the quality of life of patients. The accumulation of dysfunctional mitochondria with aging is an important factor in the occurrence and progression of sarcopenia. Mitochondrial quality control (MQC) fundamentally ensures the normal mitochondrial functions and is comprised of four main parts: proteostasis, biogenesis, dynamics and autophagy. Therefore, any pathophysiologic factors compromising the quality control of homeostasis in the skeletal muscle may lead to sarcopenia. However, the specific theoretical aspects of these processes have not been fully elucidated. Current therapeutic interventions using nutritional and pharmaceutical treatments show a modest therapeutic efficacy; however, only physical exercise is recommended as the first-line therapy for sarcopenia, which can ameliorate skeletal muscle deficiency by maintaining the homeostatic MQC. In this review, we summarized the known mechanisms that contribute to the pathogenesis of sarcopenia by impairing normal mitochondrial functions and described potential interventions that mitigate sarcopenia through improving MQC.
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OBJECTIVE: The 2019 Asian Working Group on Sarcopenia in Older People (AWGS 2019) recommends using either calf circumference or the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) or SARC-F combined with calf circumference (SARC-CalF) questionnaires for sarcopenia screening. The aim of this study was to compare the ability and applicability of calf circumference, SARC-F, and SARC-CalF for screening sarcopenia among community-dwelling older adults. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 1050 community-dwelling older people were enrolled. METHODS: Sarcopenia was diagnosed according to the AWGS 2019 criteria: bioimpedance analysis for appendicular skeletal muscle index, hand grip, and 6-m gait speed test. Participants also completed the SARC-F questionnaire and calf circumference measurement. The screening tools' performances were evaluated through receiver operating characteristic (ROC) curves, area under the ROC curves (AUC), and sensitivity/specificity analyses. RESULTS: Sarcopenia was identified in 263 (25.0%) participants by the AWGS 2019 criteria. Calf circumference had a sensitivity of 81.4% and a specificity of 77.0%. Sensitivity and specificity of SARC-F for screening sarcopenia were 17.9% and 93.7%, respectively. SARC-CalF improved the sensitivity of SARC-F (47.5%) while keeping similar specificity (92.0%). The AUCs of calf circumference, SARC-F, and SARC-CalF were 0.79 [95% confidence interval (CI), 0.77-0.82], 0.56 (95% CI, 0.52-0.59), and 0.70 (95% CI, 0.67-0.73), respectively. The differences across ROC curves were statistically significant among 3 screening tools (P < .001). CONCLUSIONS AND IMPLICATIONS: The overall screening ability of calf circumference was better than that of SARC-F and SARC-CalF for sarcopenia in community-dwelling older persons despite gender, age, and cognitive function. SARC-F and SARC-CalF have high specificity but are susceptible to the preceding factors.
Assuntos
Sarcopenia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Avaliação Geriátrica , Força da Mão , Humanos , Vida Independente , Programas de Rastreamento , Sarcopenia/diagnóstico , Inquéritos e Questionários , Velocidade de CaminhadaRESUMO
This study was the first report about complete chloroplast genome of Pertya phylicoides (Asteraceae: Pertyeae), a critically shurby plant. The complete chloroplast genome of Pertya phylicoides was 153,379 bp in length and a typical circular structure, which comprises a pair of inverted repeat (IR) region of 25,191 bp divided by a large single-copy (LSC) region of 84,535 bp and a small single-copy (SSC) region of 18,462 bp. The general GC content was 37.6% in the whole sequence, whereas corresponding values of 35.6%, 31.2%, and 43.1% in the LSC, SSC, and IR regions, respectively. The whole genome contained 113 unique genes, including 79 protein-coding genes, 4 ribosomal RNA genes, and 30 tRNA genes. The phylogenetic hypotheses obtained based on the analyses of 21 cp genomes indicates Pertya phylicoides was supported as a sister group to the tribe Carduoideae.
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It is of critical importance for our understanding of speciation process to determine the forms of reproductive isolation and their relative importance in species divergence. Oryza nivara and O. rufipogon are direct ancestors of Asian cultivated rice and a progenitor-daughter species pair. Investigating the reproductive isolation between them provides insights into plant speciation and helps understanding of the rice domestication. Here, we quantitatively measured the major components of reproductive isolation between the two species based on common garden and crossing experiments for three pairs of sympatric populations in Nepal, Cambodia and Laos. We revealed significant differences in the flowering times between species pairs, with O. nivara flowering much earlier than O. rufipogon. A very weak reduction in seed set but no reduction in F1 viability and fertility were detected for the crosses between species relative to those within species. Moreover, we detected asymmetrical compatibility between species and found that emasculation significantly decreased pollination success in O. nivara but not in O. rufipogon. Our study demonstrates that the divergence between O. nivara and O. rufipogon is maintained almost entirely by the difference in flowering times and suggests that differential flowering times contribute to both habitat preferences and reproductive isolation between species.