Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.796
Filtrar
1.
Rev. bras. med. esporte ; 29: e2022_0218, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1387963

RESUMO

ABSTRACT Introduction The CPC Central Committee and the State Council have pointed out that currently, the basic indicators of young students' physical health have completely declined. This circumstance has made adolescent physical health and improving the quality of young athletes a key issue in physical education targeting adolescents. Objective Investigate the effect of high-intensity intermittent training on young athletes. Methods 24 adolescents performed 10 intermittent high-intensity training for one month, and all athletes' pre and post-training indexes were collected and compared. Results The physical examination results of male and female athletes improved to some extent (athletes' blood pressure fluctuated during the 10 training sessions, increasing slightly, and heart rate variability increased considerably (P < 0.05). Conclusion High-intensity intermittent training has a good effect on health promotion in young athletes, and can effectively improve their physical function and competitive performance. Physical education teachers and student-athletes should conduct relevant training. In addition, this training method also fits the current learning life situation of high school students. Level of evidence II; Therapeutic studies - investigation of treatment results.


RESUMO Introdução O Comitê Central do CPC e o Conselho de Estado destacaram que, atualmente, os indicadores básicos da saúde física dos jovens estudantes têm diminuído de forma completa. Essa circunstância tornou a saúde física dos adolescentes e a melhoria da qualidade dos jovens atletas um ponto-chave na educação física direcionada aos adolescentes. Objetivo Investigar o efeito do treinamento intermitente de alta intensidade em jovens atletas. Métodos 24 adolescentes realizaram 10 treinos intermitentes de alta intensidade, com duração de um mês, todos os índices pré e pós-treino dos atletas foram coletados e comparados. Resultados Os resultados do exame físico de atletas do sexo masculino e feminino melhoraram em certa medida (a pressão arterial dos atletas flutuou durante as 10 sessões de treinamento, aumentando ligeiramente, e a variabilidade da frequência cardíaca aumentou consideravelmente (P < 0,05). Conclusão O treinamento intermitente de alta intensidade tem um bom efeito na promoção da saúde nos jovens atletas, podendo melhorar efetivamente sua função física e desempenho competitivo. Professores de educação física e atletas estudantes devem realizar treinamentos relevantes. Além disso, esse método de treinamento também se encaixa na situação atual da vida de aprendizagem dos alunos do ensino médio. Nível de evidência II; Estudos terapêuticos - investigação dos desfechos do tratamento.


RESUMEN Introducción El Comité Central del CPC y el Consejo de Estado han puesto de relieve que en la actualidad los indicadores básicos de salud física de los jóvenes estudiantes han disminuido completamente. Esta circunstancia hizo que la salud física de los adolescentes y la mejora de la calidad de los jóvenes deportistas fuera un punto clave en la educación física dirigida a los adolescentes. Objetivo Investigar el efecto del entrenamiento intermitente de alta intensidad en atletas jóvenes. Métodos 24 adolescentes realizaron 10 sesiones de entrenamiento intermitente de alta intensidad de un mes de duración, se recogieron y compararon los índices de todos los atletas antes y después del entrenamiento. Resultados Los resultados de la exploración física de los atletas masculinos y femeninos mejoraron en cierta medida (la presión arterial de los atletas fluctuó durante las 10 sesiones de entrenamiento, aumentando ligeramente, y la variabilidad de la frecuencia cardíaca aumentó considerablemente (P < 0,05). Conclusión El entrenamiento intermitente de alta intensidad tiene un buen efecto en la promoción de la salud en los atletas jóvenes, y puede mejorar eficazmente su función física y su rendimiento competitivo. Los profesores de educación física y los alumnos deportistas deben realizar la formación pertinente. Además, este método de formación también se ajusta a la situación actual de la vida de aprendizaje de los estudiantes de secundaria. Nivel de evidencia II; Estudios terapêuticos - investigación de los resultados del tratamiento.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 286: 121929, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36219963

RESUMO

Ammonia (NH3) plays a significant role in the formation of atmospheric particulate matter, and influences on environmental and public health as well as climate change. Thus, it is important to sensitive measurement of atmospheric NH3. In the present work, a sub-ppb level standoff open-path NH3 sensor was developed for on line, sensitive measurement of atmospheric NH3. A 9.06 µm distributed feedback quantum cascade laser was employed to probe the ammonia absorption lines located on fundamental rotational-vibrational absorption band and calibration-free wavelength modulation spectroscopy technique was employed to retrieve NH3 concentration directly. The standoff open-path NH3 sensor performance was investigated in laboratory corridor with 80 m open path length (Hefei, China) and a minimum detection limit of 0.46 ppb (3σ) was obtained. Finally, field campaign measurement was carried out in a winter wheat farmland (Changshu, China). Field measurement shown that the concentration of NH3 varies from 7 ppb to 30 ppb with an average of 14 ppb. The developed standoff sensor has high potential to be a robust tool for monitoring atmospheric NH3 or study of regional ammonia emissions in farmland or feedlot scale.


Assuntos
Poluentes Atmosféricos , Amônia , Monitoramento Ambiental , Análise Espectral , Estações do Ano , Calibragem , Poluentes Atmosféricos/análise
3.
Int J Food Microbiol ; 384: 109963, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36274385

RESUMO

A mixed solid matrix of the depolymerized pectin (DP) and rice protein (RP) were investigated to improve the antibacterial activity of star anise essential oil (SAEO) through microencapsulation. The encapsulation was undertaken via electrostatic complexation method followed by spray drying. Under the optimized conditions, SAEO microcapsules with 92.2 % encapsulation efficiency was acquired at 3:2 of DP-to-RP, 1:3 of DP-to-SAEO and pH 4.0. DP-RP/SAEO microcapsules exhibited a spherical-shaped particle with smaller particle size, and sustained release. FTIR and morphology analysis confirmed that SAEO was successfully encapsulated in the solid matrix of microcapsules. DP-RP/SAEO microcapsules caused the destruction of cytomembranes and reduction of membrane proteins, which led to the alteration of cell membrane fluidity and integrity. Meanwhile, DP-RP/SAEO microcapsules repressed the key enzyme in tricarboxylic acid (TCA) and Hexose monophosphate pathway (HMP) cycle pathway of E. coli, S. aureus. The application experiments indicated DP-RP/SAEO microcapsules can effectively control the growth of E. coli and S. aureus in crab meatballs.


Assuntos
Braquiúros , Illicium , Óleos Voláteis , Oryza , Animais , Cápsulas , Pectinas/farmacologia , Staphylococcus aureus , Eletricidade Estática , Escherichia coli , Antibacterianos/farmacologia , Óleos Voláteis/farmacologia
4.
Toxicol In Vitro ; 86: 105483, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36252918

RESUMO

Chlorpyrifos (CPF) is one of the most abundant and widely used organophosphate pesticides for agricultural, industrial, and household purposes in the world. Epidemiological studies have reported that CPF can induce neurotoxic impairments in mammalian, which is linked to an important risk factor for development of neurodegenerative diseases (NDs). However, limited information is available on CPF-induced neurotoxicity, with the underlying exact mechanism remains unclear. In this study, CPF exposure (10-400 µM) significantly reduced Neuro-2a cell viability and induced apoptotic events, including the increase in caspase-3 activity, apoptotic cell population, and cleavage of caspase-3/-7 and PARP. Exposure of Neuro-2a cells to CPF also triggered CHOP activation. Transfection with CHOP-specific siRNA markedly suppressed the expression of CHOP, and attenuated cytotoxicity and apoptotic events in CPF-exposed Neuro-2a cells. Furthermore, CPF exposure obviously evoked the phosphorylation of Akt as well as ROS generation in a time-dependent manner. Pretreatment with LY294002 (an Akt inhibitor) effectively attenuated the CPF-induced Akt phosphorylation, CHOP activation, and apoptotic events, but not that ROS production. Of note, buffering the ROS generation with antioxidant N-acetylcysteine effectively prevented the CPF-induced ROS generation, CHOP activation, and apoptotic events, but not that the Akt phosphorylation. Collectively, these findings indicate that CPF exposure exerts neuronal cytotoxicity via the independent pathways of ROS generation and Akt activation downstream-regulated CHOP-triggered apoptosis, ultimately leading to neuronal cell death.

5.
Carbohydr Polym ; 301(Pt A): 120299, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36436865

RESUMO

We develop a kind of photocurable liquid crystal hydrogels with bone extracellular matrix (ECM)-like liquid crystal state and viscoelasticity, as well as different chargeability. First, positively charged chitin whiskers (CHWs) and negatively charged maleic anhydride chitin whiskers (mCHWs) were prepared, which further self-assemble to form chiral nematic liquid crystals under ultrasonic treatment, respectively. Subsequently, poly (ethylene glycol) diacrylate (PEGDA) and photo initiator were added, and then two kinds of liquid crystal hydrogels with bone ECM-like viscoelasticity and different chargeability were prepared under ultraviolet (UV) irradiation. Benefiting from the bone ECM-like liquid crystal state and viscoelasticity, the prepared liquid crystal hydrogels exhibit remarkable cell affinity and osteogenic ability. Moreover, the liquid crystal hydrogel with negatively charged mCHWs is more favorable for cell adhesion, spreading and osteogenic differentiation than that with positively charged CHWs. This work provides a promising strategy to prepare the hydrogels with bone ECM-like liquid crystal properties and viscoelasticity for bone repair.


Assuntos
Hidrogéis , Cristais Líquidos , Animais , Hidrogéis/química , Quitina/química , Osteogênese , Vibrissas
6.
ACS Nano ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469414

RESUMO

Implanting a 3D printing scaffold is an effective therapeutic strategy for personalized bone repair. As the key factor for the success of bone tissue engineering, the scaffold should provide an appropriate bone regeneration microenvironment and excellent mechanical properties. In fact, the most ideal osteogenic microenvironment is undoubtedly provided by natural bone extracellular matrix (ECM), which exhibits liquid crystalline and viscoelastic characteristics. However, mimicking a bone ECM-like microenvironment in a 3D structure with outstanding mechanical properties is a huge challenge. Herein, we develop a facile approach to fabricate a bionic scaffold perfectly combining bone ECM-like microenvironment and robust mechanical properties. Creatively, 3D printing a poly(l-lactide) (PLLA) scaffold was effectively strengthened via layer-by-layer electrostatic self-assembly of chitin whiskers. More importantly, a kind of chitin whisker/chitosan composite hydrogel with bone ECM-like liquid crystalline state and viscoelasticity was infused into the robust PLLA scaffold to build the bone ECM-like microenvironment in 3D structure, thus highly promoting bone regeneration. Moreover, deferoxamine, an angiogenic factor, was encapsulated in the composite hydrogel and sustainably released, playing a long-term role in angiogenesis and thereby further promoting osteogenesis. This scaffold with bone ECM-like microenvironment and excellent mechanical properties can be considered as an effective implantation for bone repair.

7.
Cancer ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36408673

RESUMO

BACKGROUND: Antibody-drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their toxicity when applied in medical practice is of high importance. METHODS: In a systematic review and meta-analysis of data gathered from different scientific databases (PubMed, Embase, Cochrane, and Web of Science) between January 1, 2000, and June 7, 2022, the authors applied a random-effects model with logit transformation and evaluated the heterogeneity between studies using I2 statistics. The primary outcome was the incidence and 95% confidence interval (CI) for all-grade and grade ≥3 treatment-related adverse events and differences between different drugs, molecular structures, and cancer types. RESULTS: In total, 2511 records were identified that included 169 clinical trials involving 22,492 patients. The overall incidence of treatment-related adverse events was 91.2% (95% CI, 90.7%-91.7%; I2  = 95.9%) for all-grade adverse events and 46.1% (95% CI, 45.2%-47.0%; I2  = 96.3%) for grade ≥3 adverse events. The most common all-grade adverse events were lymphopenia (53.0%; 95% CI, 48.7%-57.3%), nausea (44.1%; 95% CI, 43.2%-44.9%), neutropenia (43.7%; 95% CI, 42.6%-44.9%), blurred vision (40.5%; 95% CI, 37.4%-43.6%), and peripheral neuropathy (39.6%; 95% CI, 38.2%-41.1%); and the most common grade ≥3 adverse events were neutropenia (31.2%; 95% CI, 30.2%-32.3%), hypoesthesia (23.3%; 95% CI, 10.6%-35.9%), thrombocytopenia (22.6%; 95% CI, 21.3%-23.9%), febrile neutropenia (21.2%; 95% CI, 19.3%-23.1%), and lymphopenia (21.0%; 95% CI, 18.2%-23.7%). CONCLUSIONS: Different ADCs appear to affect various treatment-related adverse events and provide comprehensive data on treatment-related adverse events for ADCs. The current results provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice. LAY SUMMARY: Unique anticancer drugs called antibody-drug conjugates (ADCs) have made significant progress in oncology in recent years because of their great success, and they are rapidly being used in the clinic as well as in hundreds of ongoing trials exploring their further use. The occurrence of serious side effects (adverse events) related to the receipt of ADCs was studied using data from 169 clinical trials involving 22,492 patients to determine the treatment-related causes of higher toxicity and adverse events in patients who receive ADCs, because these data are crucial for informing physicians how to safely treat patients using ADCs. The results indicate that different ADCs appear to affect various adverse events related to their use, providing comprehensive data on these ADCs that provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.

8.
Comput Methods Programs Biomed ; 228: 107238, 2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36423485

RESUMO

BACKGROUND AND OBJECTIVE: The assessment of the image quality is crucial before the computer-aided diagnosis of fundus images. This task is very challenging. Firstly, the subjective judgments of graders on image quality lead to ambiguous labels. Secondly, despite being treated as classification in existing works, grading has regression properties that cannot be ignored. Solving the ambiguity problem and regression problem in the label space, and extracting discriminative features, have become the keys to quality assessment. METHODS: In this paper, we proposed a framework that can assess the quality of fundus images accurately and reasonably based on deep convolutional neural networks. Drawing on the experience of human graders, a dual-path convolutional neural network with attention blocks is designed to better extract discriminative features and present the bases of decision. Label smoothing and cost-sensitive regularization are designed to solve the label ambiguity problem and the potential regression problem respectively. Besides, a large number of images are annotated by us to further improve the results. RESULTS: We conducted our experiments on the largest retinal image quality assessment dataset with 28,792 retinal images. Our approach achieves 0.8868 precision, 0.8786 recall, 0.8820 F1, and 0.9138 Kappa score. Results show that our approach outperforms state-of-the-art methods. CONCLUSIONS: The promising performances reveal that our methods are beneficial to retinal image quality assessment and have potential in other grading tasks.

9.
Front Pharmacol ; 13: 1025243, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386213

RESUMO

Background: In recent years, the rise of antibody-drug conjugates (ADCs) has changed the treatment paradigm for patients with HER2-low advanced breast cancer (ABC). DESTINY-Breast04 (NCT03734029) has demonstrated the antitumor activity of trastuzumab deruxtecan (T-DXd). However, the balance between the efficacy and cost of T-DXd remains undefined. Consequently, there is a great need to assess the cost-effectiveness of T-DXd for patients with HER2-low ABC when compared with chemotherapy. Methods: A Markov decision-analytic model with a time horizon of 15 years was employed to estimate the costs and clinical efficacy of trials with the administration of T-DXd in contrast to chemotherapy alone as a later-line therapy in a group of patients with hormone receptor-positive (HR+) or negative (HR-) HER2-low ABC. The US payer perspective was taken into account when factors such as medical lifetime expenditure, incremental cost-effectiveness ratios (ICERs), and quality-adjusted life years (QALYs) were calculated. Sensitivity analyses were used to determine the model's stability. A subgroup analysis was also conducted on the HR+/HER2-low cohort. Results: T-DXd was associated with an improvement of 0.543, 0.558, and 0.789 QALYs when compared with treatment with chemotherapy for overall, HR+, and HR- HER2-low patients, respectively. However, incorporating T-DXd into later-line therapy led to increased costs ($161,406, $177,907, and $155,757), which causes the ICER for T-DXd to be $296,873, $318,944, and $197,355 per QALY. The cost of T-DXd and the patient's weight were the most influential factors for ICER. T-DXd being the dominant strategy is about 1.5%, 0.5%, and 28.0% in overall, HR+, and HR- HER2-low ABC patients, respectively. In addition, the T-DXd regimen was not cost-effective in all subgroups. Conclusion: Compared with chemotherapy, T-DXd was not cost-effective for patients with HER2-low ABC in the United States. However, it can provide more health benefits to patients with HR+/HER2-low ABC.

10.
BMC Musculoskelet Disord ; 23(1): 979, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371192

RESUMO

BACKGROUND: Postoperative fever (POF) is a common problem after total joint arthroplasty (TJA). The goal of this research is to analyze the characteristics and risk factors of fever following TJA. METHODS: We retrospectively investigated 2482 patients who had primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) surgery at our institution between January 2020 and December 2020. Those patients were divided into TKA group and THA group. The patients' axillary temperatures were measured. POF was defined as a body temperature greater than 38 °C. Then patients in the TKA and THA groups were respectively divided into afebrile group and febrile group based on their body temperatures. Temperature changing characteristics of the patients in the febrile group were analyzed and recorded. According to the number of patients in the febrile group, we randomly selected a corresponding number of patients from the afebrile group at a ratio of 1:2 to establish a control group. Gender, hypertension, diabetes, anesthesia, surgical time, and some laboratory data were analyzed between the febrile group and the afebrile group. RESULTS: Three percent of TKA patients (N = 45) had febrile, and in the febrile group of TKA group, 38% (N = 17) had fever and maximum body temperature on postoperative day 2(POD2). Six percent of THA patients (N = 46) had fever, and in the febrile group of THA group, 65% (N = 30) of the patients had fever and maximum body temperature on POD1. In TKA group, compared with afebrile group, febrile group has higher C-reactive protein (mg/L) (CRP) after surgery. In THA group, compared with the afebrile group, the patients in the febrile group had larger fall in hemoglobin (g/L), and higher C-reactive protein (mg/L) (CRP) after surgery, so there were statistically significant differences between the two groups (P < 0.05). CONCLUSION: The POF rate of TKA is 3%, and the first fever and maximum body temperature most commonly appear on the POD2. THA has a 6% POF rate, and the first fever and the maximum body temperature most commonly appear on the POD1. In both groups, high C-reactive protein is a risk factor for postoperative fever. In addition, the fall in hemoglobin is also related to postoperative fever in the THA group.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Humanos , Estudos Retrospectivos , Proteína C-Reativa , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Fatores de Risco , Febre/diagnóstico , Febre/epidemiologia , Febre/etiologia , Hemoglobinas
11.
Nano Lett ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394551

RESUMO

Clinical serology assays for detecting the antibodies of the virus are time-consuming, are less sensitive/selective, or rely on sophisticated detection instruments. Here, we develop a sandwiched plasmonic biosensor (SPB) for supersensitive thickness-sensing via utilizing the distance-dependent electromagnetic coupling in sandwiched plasmonic nanostructures. SPBs quantitatively amplify the thickness changes on the nanoscale range (sensitivity: ∼2% nm-1) into macroscopically visible signals, thereby enabling the rapid, label-free, and naked-eye detection of targeted biomolecular species (via the thickness change caused by immunobinding events). As a proof of concept, this assay affords a broad dynamic range (7 orders of magnitude) and a low LOD (∼0.3 pM), allowing for the extremely accurate SARS-CoV-2 antibody quantification (sensitivity/specificity: 100%/∼99%, with a portable optical fiber device). This strategy is suitable for high-throughput multiplexed detection and smartphone-based sensing at the point-of-care, which can be expanded for various sensing applications beyond the fields of viral infections and vaccination.

12.
World J Clin Cases ; 10(32): 11955-11966, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36405262

RESUMO

BACKGROUND: Aplastic anemia (AA) complicated with myocardial infarction (MI) is rare and associated with poor prognosis. Here, we present a case of AA with recurrent acute MI (AMI) in a patient treated with cyclosporine A (CsA) and stanozolol. In this patient, we suspect the long-term use of medication linked to platelets hyperfunction. CASE SUMMARY: In 2017, a 45-year-old man was rushed to the emergency department of China-Japan Union Hospital due to precordial pain for 5 h. Based on his symptoms, medical history, blood tests, and findings from coronary angiography (CAG), the patient was diagnosed with acute anterior wall, ST-segment elevated MI, Killip II grade, AA, and dyslipidemia. In 2021, the patient was readmitted to the hospital for 2 h due to chest pain. Because the patient's platelet count was 30 × 109/L and he had severe thrombocytopenia, we performed CAG following platelet transfusion. Optical coherence tomography revealed lipid plaque and thrombus mass in his right coronary artery. The antithrombotic approach was adjusted to employ only anticoagulants (factor Xa inhibitors) and adenosine diphosphate inhibitors (clopidogrel) after assessing the risk of bleeding/thrombotic events. Long-term follow-up revealed that the patient had made a good recovery. CONCLUSION: Patients with AA should be closely monitored for the risk of thrombosis and cardiovascular events, particularly when taking stanozolol or CsA for an extended period of time.

13.
Elife ; 112022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36399125

RESUMO

Cardiovascular disease is the leading cause of death worldwide due to the inability of adult heart to regenerate after injury. N6-methyladenosine (m6A) methylation catalyzed by the enzyme methyltransferase-like 3 (Mettl3) plays an important role in various physiological and pathological bioprocesses. However, the role of m6A in heart regeneration remains largely unclear. To study m6A function in heart regeneration, we modulated Mettl3 expression in vitro and in vivo. Knockdown of Mettl3 significantly increased the proliferation of cardiomyocytes and accelerated heart regeneration following heart injury in neonatal and adult mice. However, Mettl3 overexpression decreased cardiomyocyte proliferation and suppressed heart regeneration in postnatal mice. Conjoint analysis of methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq identified Fgf16 as a downstream target of Mettl3-mediated m6A modification during postnatal heart regeneration. RIP-qPCR and luciferase reporter assays revealed that Mettl3 negatively regulates Fgf16 mRNA expression in an m6A-Ythdf2-dependent manner. The silencing of Fgf16 suppressed the proliferation of cardiomyocytes. However, the overexpression of ΔFgf16, in which the m6A consensus sequence was mutated, significantly increased cardiomyocyte proliferation and accelerated heart regeneration in postnatal mice compared with wild-type Fgf16. Our data demonstrate that Mettl3 post-transcriptionally reduces Fgf16 mRNA levels through an m6A-Ythdf2-dependen pathway, thereby controlling cardiomyocyte proliferation and heart regeneration.


Cardiovascular diseases are one of the world's biggest killers. Even for patients who survive a heart attack, recovery can be difficult. This is because ­ unlike some amphibians and fish ­ humans lack the ability to produce enough new heart muscle cells to replace damaged tissue after a heart injury. In other words, the human heart cannot repair itself. Molecules known as messenger RNA (mRNA) carry the 'instructions' from the DNA inside the cell nucleus to its protein-making machinery in the cytoplasm of the cell. These messenger molecules can also be altered by different enzymes that attach or remove chemical groups. These modifications can change the stability of the mRNA, or even 'silence' it altogether by stopping it from interacting with the protein-making machinery, thus halting production of the protein it encodes. For example, a protein called Mettl3 can attach a methyl group to a specific part of the mRNA, causing a reversible mRNA modification known as m6A. This type of alteration has been shown to play a role in many conditions, including heart disease, but it has been unclear whether m6A could also be important for the regeneration of heart tissue. To find out more, Jiang, Liu, Chen et al. studied heart injury in mice of various ages. Newborn mice can regenerate their heart muscle for a short time, but adult mice lack this ability, which makes them a useful model to study heart disease. Analyses of the proteins and mRNAs in mouse heart cells confirmed that both Mettl3 and m6A-modified mRNAs were present. The amount of each also increased with age. Next, experiments in genetically manipulated mice revealed that removing Mettl3 greatly improved tissue repair after heart injury in both newborn and adult mice. In contrast, mouse hearts that produced abnormally high quantities of Mettl3 were unable to regenerate ­ even if the mice were young. Moreover, a detailed analysis of gene activity revealed that Mettl3 was suppressing heart regeneration by decreasing the production of a growth-promoting protein called FGF16. These results reveal a key biological mechanism controlling the heart's ability to repair itself after injury. In the future, Jiang et al. hope that Mettl3 can be harnessed for new, effective therapies to promote heart regeneration in patients suffering from heart disease.


Assuntos
Metiltransferases , Miócitos Cardíacos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , RNA Mensageiro/metabolismo , Metilação , Fatores de Transcrição/metabolismo , Proliferação de Células
14.
World J Oncol ; 13(5): 272-288, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36406198

RESUMO

Background: Vincosamide (Vinco) was first identified in the methanolic extract of the leaves of Psychotria leiocarpa, and Vinco has important anti-inflammatory effects and activity against cholinesterase, Vinco also has a trait to anti-tumor. However, whether Vinco can inhibit the malignant behaviors of hepatocellular carcinoma (HCC) cells is still unclear. In the present study, we explored the role of Vinco in suppressing the malignant behaviors of HCC cells. Methods: MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide), trypan blue exclusion assay, the Cell Counting Kit (CCK)-8 and flow cytometric analysis were applied to detect the proliferation and apoptosis of HCC cells; electron microscopy was performed to observe the change of cellular mitochondrial morphology; scratch repair and Transwell assays were used to analyze the migration and invasion of HCC cells; expression and localization of proteins were detected by laser confocal microscopy and Western blotting; the growth of the cancer cells in vivo was assessed in a mouse tumorous model. Results: At a dose of 10 - 80 µg/mL, Vinco inhibited the proliferation, migration, invasion and promoted apoptosis of HCC cells in a dose-dependent manner but had low cytotoxicity effect on normal liver cells. Additionally, 80 µg/mL of Vinco could significantly disrupt the morphology of mitochondria, suppress the migration and invasion of HCC cells. The growth of HCC cells in the animal tumorous model was significantly inhibited after treatment with Vinco (10 mg/kg/day) for 3 days. The results of the present study indicated that Vinco (10 - 80 µg/mL) played a role in activating caspase-3, promoting the expression of phosphate and tension homology deleted on chromosome 10 (PTEN), and inhibiting the phosphorylation of AKT (Ser473) and mTOR (Thr2448); Vinco also has a trait for suppressing the expression of CXCR4, Src, MMP9, EpCAM, Ras, Oct4 and cancer stem cell "stemness markers" CD133 and CD44 in HCC cells. Conclusions: Vinco has a role in inhibiting the malignant behaviors of HCC cells; the role molecular mechanism of Vinco may be involved in restraining expression of the growth-, metastasis-related factors, such as Src, Ras, MMP9, EpCAM, CXCR4; activating the activity of caspase-3 and blocking PI3K/AKT signaling pathway. Thus, Vinco should be considered as a new chemotherapy agent for HCC patients.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36412196

RESUMO

BACKGROUND: Elevated plasma Lp-PLA2 (lipoprotein-associated phospholipase A2) activity is closely associated with an increased risk of cardiovascular events. However, whether and how Lp-PLA2 is directly involved in the pathogenesis of atherosclerosis is still unclear. To examine the hypothesis that Lp-PLA2 could be a potential preventative target of atherosclerosis, we generated Lp-PLA2 knockout rabbits and investigated the pathophysiological functions of Lp-PLA2. METHODS: Lp-PLA2 KO rabbits were generated using CRISPR/Cas9 system to assess the role of Lp-PLA2 in plasma lipids regulation and identify its underlying molecular mechanisms. Homozygous knockout rabbits along with wild-type rabbits were fed a cholesterol-rich diet for up to 14 weeks and their atherosclerotic lesions were compared. Moreover, the effects of Lp-PLA2 deficiency on the key cellular behaviors in atherosclerosis were assessed in vitro. RESULTS: When rabbits were fed a standard diet, Lp-PLA2 deficiency led to a significant reduction in plasma lipids. The decreased protein levels of SREBP2 (sterol regulatory element-binding protein 2) and HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) in livers of homozygous knockout rabbits indicated that the cholesterol biosynthetic pathway was impaired with Lp-PLA2 deficiency. In vitro experiments further demonstrated that intracellular Lp-PLA2 efficiently enhanced SREBP2-related cholesterol biosynthesis signaling independently of insulin-induced genes (INSIGs). When fed a cholesterol-rich diet, homozygous knockout rabbits exhibited consistently lower level of hypercholesterolemia, and their aortic atherosclerosis lesions were significantly reduced by 60.2% compared with those of wild-type rabbits. The lesions of homozygous knockout rabbits were characterized by reduced macrophages and the expression of inflammatory cytokines. Macrophages of homozygous knockout rabbits were insensitive to M1 polarization and showed reduced DiI-labeled lipoprotein uptake capacity compared with wild-type macrophages. Lp-PLA2 deficiency also inhibited the adhesion between monocytes and endothelial cells. CONCLUSIONS: These results demonstrate that Lp-PLA2 plays a causal role in regulating blood lipid homeostasis and Lp-PLA2 deficiency protects against dietary cholesterol-induced atherosclerosis in rabbits. Lp-PLA2 could be a potential target for the prevention of atherosclerosis.

16.
J Thorac Dis ; 14(10): 3934-3954, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36389336

RESUMO

Background: Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors worldwide. Lung adenocarcinoma (LUAD), the main subtype of NSCLC, has a poor prognosis. In recent years, circadian rhythm (CR)-related genes (CRRGs) have demonstrated associations with tumor occurrence and development, but the relationship between CRRGs and LUAD is not clear. Because of the correlation between CRRGs and tumors, we have reason to believe that CRRGs will become an important prognostic indicator for LUAD and guide the treatment of LUAD prognosis. Methods: Based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we explored the biological function and immune cell infiltration of LUAD in different CR clusters and quantified CR genes using principal component analysis (PCA). Then, we built a CR scoring system (CRscore) to explore the relationship between CRRGs and LUAD prognosis. Results: Patients were divided into three clusters (A, B, and C). Biological characteristics, such as survival, immune cell infiltration, and gene enrichment, were significantly different among the three clusters (P<0.001). We then established the usefulness of the CR score, which could probably predict the prognosis of LUAD. Specifically, patients with a high CR score had a better prognosis and were more sensitive to chemotherapy than those with a low CR score. Conclusions: It is possible to use CRRGs to assess the prognosis of patients with LUAD. Quantification of CR using the CRscore tool in patients with LUAD maybe help to guide personalized cancer immunotherapy strategies in the future. Thus, the CRscore may be a prognostic tool for LUAD.

17.
ACS Synth Biol ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36416371

RESUMO

As a natural biological macromolecule, γ-polyglutamic acid (γ-PGA) plays a significant role in medicine, food, and cosmetic industries owing to its unique properties of biocompatibility, biodegradability, water solubility, and viscosity. Although many strategies have been adopted to increase the yield of γ-PGA in Bacillus subtilis, the effectiveness of these common approaches is not high because the strong viscosity affects cell growth. However, dynamic regulation based on quorum sensing (QS) has been extensively applied as a fundamental tool for fine-tuning gene expression in reaction to changes in cell density without adding expensive inducers. A modular PhrQ-RapQ-DegU QS system is developed based on promoter PD4, which is upregulated by phosphorylated DegU (DegU-P). In this study, first, we analyzed the DegU-based gene expression regulation system in B. subtilis 168. We constructed a promoter library of different abilities, selected suitable promoters from the library, and performed mutation screening on the selected promoters and degU region. Furthermore, we constructed a PhrQ-RapQ-DegU QS system to dynamically control the synthesis of γ-PGA in BS168. Cell growth and efficient synthesis of the target product can be dynamically balanced by the QS system. Our dynamic adjustment approach increased the yield of γ-PGA to 6.53-fold of that by static regulation in a 3 L bioreactor, which verified the effectiveness of this strategy. In summary, the PhrQ-RapQ-DegU QS system has been successfully integrated with biocatalytic functions to achieve dynamic metabolic pathway control in BS168, which can be stretched to a large number of microorganisms to fine-tune gene expression and enhance the production of metabolites.

18.
Nano Lett ; 22(22): 9006-9012, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36342788

RESUMO

Inducing structural changes and deformation using noninvasive methods, such as ultrafast laser technology, is an attractive route to multiple optomechanical and optoelectronic applications. Here, we show how photon excitation could accumulate in-plane stress and induce long-wavelength ripples in two-dimensional (2D) materials. Numerical results based on first-principles calculations and a continuum model predict that long-range nanoscale rippling could emerge under photon excitation in hexagonal nitride single atomic sheets. The photosoftened transverse acoustic mode dominates the out-of-plane distortion of the sheet, and the resultant rippling pattern strongly depends on the boundary condition. We reveal that the wavelength and height of the ripple scale as I-1/3 and I1/6, respectively, where I is the incident light energy flux. Our findings based on multiscale theory and simulations elucidate the interplay between carrier excitation, phonon dispersion, and long-range mechanical deformations, which could find potential usage in flexible electronics and electromechanical devices.

19.
Breast ; 66: 191-198, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36327624

RESUMO

BACKGROUND: DESTINY-Breast03 (NCT03529110) was the first global phase III study to assess the antitumor activity of trastuzumab deruxtecan (T-DXd) compared to trastuzumab emtansine (T-DM1) in 2022. However, the balance between efficacy and cost of T-DXd remains unclear. As a result, the present study's goal is to investigate the cost-effectiveness of T-DXd vs T-DM1 as a second-line treatment for patients with HER2-positive MBC from the US and Chinese payer's perspectives. METHODS: A Markov model with a 20-year time horizon was developed to evaluate the overall cost of patient treatment, incremental cost-effectiveness ratio (ICER), quality-adjusted life-years (QALYs), and life-years (LYs) in the US and China at WTP levels of 150,000/QALY and 37,653/QALY, respectively (3 times GDP per capita in 2021). Key data were gathered from the US government's official website, the Xiangya Hospital of Central South University, and published literature. To determine the model's stability, a sensitivity analysis was performed. A subgroup analysis was also implemented. RESULTS: Compared with T-DM1, treatment with T-DXd generated an additional 1.672 QALYs (2.796 LYs), resulting in an ICER of $13,342/QALY (US) and $186,017/QALY (China). The cost of drugs is the most influential factor in the American and Chinese models. Subgroup analysis revealed that the T-DXd and T-DM1 regimens were more cost-effective at reducing the risk of death in the US and Chinese HER2-positive MBC patients. CONCLUSION: T-DXd as second-line treatment could gain more health benefits for HER2-positive MBC patients in comparison with T-DM1, which is considered to be cost-effective in the US but not in China.

20.
Animals (Basel) ; 12(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36359082

RESUMO

Beta-defensin-1 (BD-1) is among the class of antibacterial peptides that are rich in disulfide bonds, have direct antibacterial activity and showed enhanced expression following external stimulation. However, existing research studies only treated BD-1 to cell models without stimulation from pathogen-associated molecular patterns (PAMPs), which will further influence our understanding of the role of BD-1. In this study, we map the tissue distribution of Equus BD-1 (i.e., eBD-1, ass BD-1, and mule BD-1) and compare their expression levels in various tissues. We further characterize the three kinds of Equus BD-1 by analyzing their full-length cDNA. We showed that eBD-1, ass BD-1, and mule BD-1 have an identical (100%) open reading frame (ORF). The ORF encoding OEBD-1 expressed the ORF in the E. coli Top10 expression system. This expression system was combined with an S. aureus-infected J774A.1 macrophage cell line to determine the influence on innate immune mediator expression. Using this expression model system, it was determined that the OEBD-1 protein enhanced IL-6 and TNF-α secretion. It can also promote TLR2, IL-1ß, CCL2, CCL7, CXCL10 and NF-κB p65 mRNA expression. Moreover, OEBD-1 upregulates phosphorylation of ATK, Syk and IκB-α. In addition, OEBD-1 enhances the macrophage's ability to phagocytose S. aureus. In conclusion, Equus BD-1 was shown to play an essential role in macrophage-involved innate immune responses in an in vitro system.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...