Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
1.
Lancet Reg Health West Pac ; 45: 100992, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38699293

RESUMO

Over the last 20 years, the numbers, types, distribution, and qualifications of mental health professionals in China have changed dramatically. However, there has been no systematic attempt to collect information about this transformation in the human resources available to provide mental health services-information that needs to be regularly updated to improve the country's coordination of these services. This scoping review compiles current details about China's mental health workforce and identifies critical gaps in available research and reporting. We reviewed all relevant studies and reports published between 1 January 2000 and 30 June 2021 in two English-language and four Chinese-language databases, the website of China's National Health Commission, and national and provincial health services yearbooks. In addition to summarising data from government yearbooks, we integrated relevant results from 82 peer-reviewed publications and two government reports. From 2000 to 2020, the number of psychiatrists in the country increased by 139%, and the number of psychiatric nurses increased by 340%. However, the much higher ratio of mental health professionals per 100,000 population and the better quality of training of mental health professionals in urban, eastern provinces compared to rural, western provinces has not changed. Progress has been made in standardising the training of psychiatrists, but there are no standardised training programs for psychiatric nurses, clinical psychologists, or psychiatric social workers. Future research needs to address several issues that limit the effectiveness of policies aimed at increasing the size, quality and equitable distribution of China's mental health workforce: 1) limited data available about the numbers and characteristics of professionals who provide mental health services, 2) absence of nationally standardised training programs for non-psychiatric medical professionals and non-medical personnel who provide essential monitoring and supportive care to persons with mental illnesses, and 3) failure to scientifically assess the outcomes of currently available training programs.

2.
Nanomaterials (Basel) ; 14(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38668167

RESUMO

Solid oxide fuel cells (SOFCs) offer a significant advantage over other fuel cells in terms of flexibility in the choice of fuel. Ammonia stands out as an excellent fuel choice for SOFCs due to its easy transportation and storage, carbon-free nature and mature synthesis technology. For direct-ammonia SOFCs (DA-SOFCs), the development of anode catalysts that have efficient catalytic activity for both NH3 decomposition and H2 oxidation reactions is of great significance. Herein, we develop a Mo-doped La0.6Sr0.4Fe0.8Ni0.2O3-δ (La0.6Sr0.4Fe0.7Ni0.2Mo0.1O3-δ, LSFNM) material, and explore its potential as a symmetrical electrode for DA-SOFCs. After reduction, the main cubic perovskite phase of LSFNM remained unchanged, but some FeNi3 alloy nanoparticles and a small amount of SrLaFeO4 oxide phase were generated. Such reduced LSFNM exhibits excellent catalytic activity for ammonia decomposition due to the presence of FeNi3 alloy nanoparticles, ensuring that it can be used as an anode for DA-SOFCs. In addition, LSFNM shows high oxygen reduction reactivity, indicating that it can also be a cathode for DA-SOFCs. Consequently, a direct-ammonia symmetrical SOFC (DA-SSOFC) with the LSFNM-infiltrated doped ceria (LSFNM-SDCi) electrode delivers a superior peak power density (PPD) of 487 mW cm-2 at 800 °C when NH3 fuel is utilised. More importantly, because Mo doping greatly enhances the reduction stability of the material, the DA-SSOFC with the LSFN-MSDCi electrode exhibits strong operational stability without significant degradation for over 400 h at 700 °C.

3.
Crit Care ; 28(1): 122, 2024 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616271

RESUMO

BACKGROUND: The relationship between smoking and the risk of acute respiratory distress syndrome (ARDS) has been recognized, but the conclusions have been inconsistent. This systematic review and meta-analysis investigated the association between smoking and ARDS risk in adults. METHODS: The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies published from January 1, 2000, to December 31, 2023. We enrolled adult patients exhibiting clinical risk factors for ARDS and smoking condition. Outcomes were quantified using odds ratios (ORs) for binary variables and mean differences (MDs) for continuous variables, with a standard 95% confidence interval (CI). RESULTS: A total of 26 observational studies involving 36,995 patients were included. The meta-analysis revealed a significant association between smoking and an increased risk of ARDS (OR 1.67; 95% CI 1.33-2.08; P < 0.001). Further analysis revealed that the associations between patient-reported smoking history and ARDS occurrence were generally similar to the results of all the studies (OR 1.78; 95% CI 1.38-2.28; P < 0.001). In contrast, patients identified through the detection of tobacco metabolites (cotinine, a metabolite of nicotine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of tobacco products) showed no significant difference in ARDS risk (OR 1.19; 95% CI 0.69-2.05; P = 0.53). The smoking group was younger than the control group (MD - 7.15; 95% CI - 11.58 to - 2.72; P = 0.002). Subgroup analysis revealed that smoking notably elevated the incidence of ARDS with extrapulmonary etiologies (OR 1.85; 95% CI 1.43-2.38; P < 0.001). Publication bias did not affect the integrity of our conclusions. Sensitivity analysis further reinforced the reliability of our aggregated outcomes. CONCLUSIONS: There is a strong association between smoking and elevated ARDS risk. This emphasizes the need for thorough assessment of patients' smoking status, urging healthcare providers to vigilantly monitor individuals with a history of smoking, especially those with additional extrapulmonary risk factors for ARDS.


Assuntos
Síndrome do Desconforto Respiratório , Fumar , Adulto , Humanos , Reprodutibilidade dos Testes , Fumar/efeitos adversos , Fumar/epidemiologia , Fatores de Risco , 1-Butanol , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/etiologia
4.
Front Med (Lausanne) ; 11: 1354489, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515989

RESUMO

Background: Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) often coexist, and the causal relationship between them is not yet clear; treatments for OSA include continuous positive airway pressure (CPAP), mandibular advancement device (MAD), surgery, and lifestyle intervention and so on. However, the effects of different treatments on metabolic syndrome in OSA patients are still under debate. Objectives: Review the effects of different treatments on metabolic syndrome in OSA patients by meta-analysis. Methods: we searched articles in PubMed, Embase, Cochrane Library, CNKI, CBM, and Wanfang data from database construction to Feb. 2024.RevMan5.4 and Stata software were used to conduct a meta-analysis of 22 articles. Results: A total of 22 articles were finally included. The results showed that CPAP treatment could reduce the prevalence of metabolic syndrome in OSA patients in randomized controlled trials (RCTs) (RR = 0.82 [95% CI, 0.75 to 0.90]; p < 0.01) and single-arm studies (RR = 0.73 [95% CI, 0.63 to 0.84]; p < 0.01). As for metabolic syndrome components, CPAP treatment reduces blood pressure, fasting glucose (FG), triglycerides (TG), and waist circumference (WC) but can't affect high-density lipoprotein cholesterol (HDL-C) levels. Lifestyle intervention could significantly reduce the prevalence of metabolic syndrome in OSA patients (RR = 0.60 [95% CI, 0.48 to 0.74]; p < 0.01) and can lower blood pressure, fasting glucose, and waist circumference but can't affect the lipid metabolism of OSA patients. Upper airway surgery can only reduce TG levels in OSA patients (MD = -0.74 [95% CI, -1.35 to -0.13]; p = 0.02) and does not affect other components of metabolic syndrome. There is currently no report on the impact of upper airway surgery on the prevalence of metabolic syndrome. No study has reported the effect of MAD on metabolic syndrome in OSA patients. Conclusion: We confirmed that both CPAP and lifestyle intervention can reduce the prevalence of MetS in OSA patients. CPAP treatment can lower blood pressure, fasting glucose, waist circumference, and triglyceride levels in OSA patients. Lifestyle intervention can lower blood pressure, fasting glucose, and waist circumference in OSA patients. Upper airway surgery can only reduce TG levels in OSA patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022326857.

5.
Cytotherapy ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38520411

RESUMO

BACKGROUND AIMS: Rheumatoid arthritis (RA) is characterized by an overactive immune system, with limited treatment options beyond immunosuppressive drugs or biological response modifiers. Human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) represent a novel alternative, possessing diverse immunomodulatory effects. In this study, we aimed to elucidate the therapeutic effects and underlying mechanisms of hESC-MSCs in treating RA. METHODS: MSC-like cells were differentiated from hESC (hESC-MSCs) and cultured in vitro. Cell proliferation was assessed using Cell Counting Kit-8 assay and Ki-67 staining. Flow cytometry was used to analyze cell surface markers, T-cell proliferation and immune cell infiltration. The collagen-induced arthritis (CIA) mouse model and bleomycin-induced model of lung fibrosis (BLE) were established and treated with hESC-MSCs intravenously for in vivo assessment. Pathological analyses, reverse transcription-quantitative polymerase chain reaction and Western blotting were conducted to evaluate the efficacy of hESC-MSCs treatment. RESULTS: Intravenous transplantation of hESC-MSCs effectively reduced inflammation in CIA mice in this study. Furthermore, hESC-MSC administration enhanced regulatory T cell infiltration and activation. Additional findings suggest that hESC-MSCs may reduce lung fibrosis in BLE mouse models, indicating their potential to mitigate complications associated with RA progression. In vitro experiments revealed a significant inhibition of T-cell activation and proliferation during co-culture with hESC-MSCs. In addition, hESC-MSCs demonstrated enhanced proliferative capacity compared with traditional primary MSCs. CONCLUSIONS: Transplantation of hESC-MSCs represents a promising therapeutic strategy for RA, potentially regulating T-cell proliferation and differentiation.

6.
Plant Cell ; 36(5): 1892-1912, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38262703

RESUMO

In cereal grains, starch is synthesized by the concerted actions of multiple enzymes on the surface of starch granules within the amyloplast. However, little is known about how starch-synthesizing enzymes access starch granules, especially for amylopectin biosynthesis. Here, we show that the rice (Oryza sativa) floury endosperm9 (flo9) mutant is defective in amylopectin biosynthesis, leading to grains exhibiting a floury endosperm with a hollow core. Molecular cloning revealed that FLO9 encodes a plant-specific protein homologous to Arabidopsis (Arabidopsis thaliana) LIKE EARLY STARVATION1 (LESV). Unlike Arabidopsis LESV, which is involved in starch metabolism in leaves, OsLESV is required for starch granule initiation in the endosperm. OsLESV can directly bind to starch by its C-terminal tryptophan (Trp)-rich region. Cellular and biochemical evidence suggests that OsLESV interacts with the starch-binding protein FLO6, and loss-of-function mutations of either gene impair ISOAMYLASE1 (ISA1) targeting to starch granules. Genetically, OsLESV acts synergistically with FLO6 to regulate starch biosynthesis and endosperm development. Together, our results identify OsLESV-FLO6 as a non-enzymatic molecular module responsible for ISA1 localization on starch granules, and present a target gene for use in biotechnology to control starch content and composition in rice endosperm.


Assuntos
Endosperma , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Amido , Oryza/genética , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Endosperma/metabolismo , Endosperma/genética , Amido/metabolismo , Amido/biossíntese , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Amilopectina/metabolismo , Mutação , Plantas Geneticamente Modificadas
7.
Biotechnol J ; 19(1): e2200632, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37735964

RESUMO

There are few effective treatment options for diffuse pulmonary hemorrhage (DPH). We aimed to elucidate the therapeutic role and underlying mechanisms of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) in DPH. Therapeutic effects of MSCs/MSC-EVs in pristane-induced DPH mice were evaluated via pulmonary function testing and histopathology. Transcriptome sequencing analyzed differentially expressed genes in control, DPH, and MSC groups. The proportion of macrophage polarization was evaluated in vivo and in vitro via fluorescence-activated cell sorting in control, DPH, MSC, MSC-EV inhalation, and MSC-EV intravenous groups. Intraperitoneal injection of pristane induced diffuse alveolar hemorrhage, early fibrosis, and inflammation in C57BL/6 mice. Monocytes were depleted in the peripheral blood in DPH mice and MSCs were recruited to the lungs, resulting in significantly attenuated diffuse alveolar hemorrhage and suppressed immunological response. This was more effective in the hyperacute hemorrhage phase than the early inflammatory phase. An MSC treatment-mediated anti-inflammatory effect was observed in DPH mice. Furthermore, MSC-EVs inhalation or tail-vein injection could effectively reduce DPH injury. MSCs could suppress macrophage M1 polarization in DPH in vivo and in vitro. MSCs displayed significant therapeutic effects in pristane-induced DPH, which may be a promising cell-free therapeutic approach.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Terpenos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Pulmão/patologia , Hemorragia/terapia , Hemorragia/patologia , Anti-Inflamatórios , Células-Tronco Mesenquimais/fisiologia , Modelos Animais de Doenças
8.
Psychiatry Res ; 329: 115517, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37826974

RESUMO

Suicide has aroused global concern, and a better understanding of the complex interactions between suicide ideation and various psychopathological features is critical. We aimed to explore the complex interplays among adolescents. This study adopted a multistage stratified cluster sampling method and recruited adolescents aged 12 to 20 year-old from 8 middle and high schools between December 2020 and September 2021 in Guangzhou, China. We assessed loneliness, social support, bullying victimization, depressive symptoms, and suicidal ideation. We used network analysis to examine the network structure of the correlates of suicidal ideation and identify central symptoms and bridge symptoms. We used case-drop bootstrapping and correlation stability coefficients to examine the stability of the network. Among 8686 adolescents, 347 (4 %) adolescents reported suicidal ideation in the past two weeks. Network analyses identified 'hopeless', 'psychomotor', and 'failure' were the three strongest edges linked to suicidal ideation. The most central nodes were identified as 'hopeless' being the most central node, followed by loneliness and verbal bullying victimization, while sexual bullying victimization, sex, and relational bullying were the strongest bridging symptoms. The findings shed light on the complexity of associations of suicidal ideation and could provide insight into school-based suicide risk assessment and prevention for adolescents.


Assuntos
Bullying , Vítimas de Crime , Humanos , Adolescente , Criança , Adulto Jovem , Adulto , Ideação Suicida , Depressão , Vítimas de Crime/psicologia , Afeto
9.
J Colloid Interface Sci ; 642: 736-746, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37037079

RESUMO

Carbon morphology significantly affects the capacitive performance of porous carbons. Biomass-derived porous carbons are usually restricted by inferior capacitive performance owing to their inherently three-dimensional (3D) blocked morphologies. Fabricating two-dimensional (2D) sheet-like morphology is expected to expose more inner space for better electrochemical performance, however, it needs to overcome the self-aggregation of biomass. The comprehensive understanding of how 2D morphology boosts capacitive performance remains challenging. Herein, we provide a morphology-regulating strategy to prepare 2D and 3D porous carbons and investigate the morphology effect on charge storage capability via both experimental data and theoretical simulations. 2D carbon exhibits better capacitance than 3D carbon in both electric double-layer capacitors (254 versus 211F g-1) and zinc-ion hybrid supercapacitors (320 versus 232F g-1), because the 2D carbon morphology not only improves the pore accessibility for higher double-layer capacitance, but also facilitates the exposure of active functional groups for more pseudocapacitance. Moreover, 2D morphology shortens pore length, leading to better anti-self-discharge capability. This study is beneficial to understanding the relationship between carbon morphology and capacitive performance and provides a facile strategy to upgrade biomass-derived porous carbons via morphology engineering.

10.
Bioorg Chem ; 135: 106488, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36989734

RESUMO

Abnormal activation of Hedgehog (Hh) signaling pathway mediates the genesis and progression of various tumors [1]. Currently, three drugs targeting the Hh signaling component Smoothened (Smo) have been marketed for the clinical treatment of basal cell tumors or acute myeloid leukemia. However, drug resistance is a common problem in those drugs, so the study of Smo inhibitors that can overcome drug resistance has important guiding significance for clinical adjuvant drugs. MTT assay, clone formation assay and EdU assay were used to detect the proliferation inhibitory activity of the drugs on tumor cells. The effect of B13 on cell cycle and apoptosis were detected by flow cytometry. An acute toxicity test was used to detect the toxicity of B13 in vivo, and xenograft tumor model was used to detect the efficacy of B13 in vivo. The binding of B13 to Smo was studied by BODIPY-cyclopamine competitive binding assay and molecular docking. The effect of B13 on the expression and localization of downstream target gene Gli1/2 of Smo was investigated by Western Blot and immunofluorescence assay. SmoD473H mutant cell line was constructed to study the effect of B13 against drug resistance. (1) B13 had the strongest inhibitory activity against colorectal cancer cells. (2) B13 can effectively inhibit the clone formation and EdU positive rate of colon cancer cells. (3) B13 can block the cell cycle in the G2/M phase and cell apoptosis. (4) B13 has low toxicity in vivo, and its efficacy in vivo is better than that of the Vismodegib. (5) Molecular docking and BODIPY-cyclopamine experiments showed that B13 could bind to Smo protein. (6) B13 can inhibit the protein expression of Gli1, the downstream of Smo, and inhibit its entry into the nucleus. (7) B13 could inhibit the expression of Gli1 in the HEK293 cells with SmoD473H, and the molecular docking results showed that B13 could bind SmoD473H protein. B13 with the best anti-tumor activity was screened out by MTT assay. In vitro, pharmacodynamics experiments showed that B13 could effectively inhibit the proliferation and metastasis of colorectal cancer cells, induce cell cycle arrest, and induce cell apoptosis. In vivo pharmacodynamics experiments showed that B13 was superior to Vismodegib in antitumor activity and had low toxicity in vivo. Mechanism studies have shown that B13 can bind Smo protein, inhibit the expression of downstream Gli1 and its entry into the nucleus. Notably, B13 overcomes resistance caused by SmoD473H mutations.


Assuntos
Neoplasias Colorretais , Proteínas Hedgehog , Humanos , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Proteína GLI1 em Dedos de Zinco/farmacologia , Células HEK293 , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Proliferação de Células
11.
Immunopharmacol Immunotoxicol ; 45(5): 549-557, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36942663

RESUMO

BACKGROUND AND AIMS: Mesenchymal stem cell (MSC) therapy is a promising strategy for treating osteoarthritis (OA). However, the inflammatory microenvironment, apoptosis of transplanted cells, and shear forces during direct injection limit the therapeutic efficacy. This study aimed to explore the role of rapamycin combined with human umbilical-cord-derived mesenchymal stem cells (hUMSCs) in OA rabbits in vivo. METHODS: OA rabbits received an intra-articular injection of a collagenase solution. Gross observations, X-ray examinations, and histological examinations were performed to detect cartilage degradation levels. The fluorescent membrane dye DiR was used to label hUMSCs. In the combination therapy group, rapamycin was injected into the rabbit knee joint one day post the intra-articular injection of hUMSCs. Bioinformatics and transcriptome profiling of the knee meniscus were used to evaluate the potential molecular mechanisms of the combination therapy. RESULTS: Our study shows that rapamycin combined with hUMSCs significantly ameliorated OA severity in vivo, enhancing matrix synthesis and promoting cartilage repair. The combination therapy was more efficient than rapamycin or hUMSC treatment alone. Moreover, bioinformatics and transcriptomic analyses revealed that combination therapy might enhance autophagy in chondrocytes, partially by inhibiting the mTOR pathway. CONCLUSIONS: Our study indicates that the combination therapy of rapamycin and hUMSCs may promote cartilage repair in OA rabbits through the mTOR pathway and offers a novel approach for OA therapy. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study provides new evidence to support the use of hUMSCs in combination with rapamycin as a potential candidate for OA treatment.


Assuntos
Cartilagem Articular , Células-Tronco Mesenquimais , Osteoartrite , Animais , Humanos , Coelhos , Sirolimo/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cartilagem Articular/metabolismo , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Osteoartrite/metabolismo , Células-Tronco Mesenquimais/metabolismo
12.
Biomater Res ; 26(1): 66, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435848

RESUMO

BACKGROUND: As an emerging therapeutic modality, chemodynamic therapy (CDT), converting hydrogen peroxide (H2O2) into highly toxic reactive oxygen species (ROS), has been developed for tumor-specific therapy. However, the deficiency of endogenous H2O2 and high concentration of glutathione (GSH) in the tumor microenvironment (TME) weaken the CDT-based tumor-therapeutic efficacy. Herein, a photothermal-enhanced tumor-specific cascade catalytic nanosystem has been constructed on the basis of glucose oxidase (GOD)-functionalized molybdenum (Mo)-based polyoxometalate (POM) nanoclusters, termed as GOD@POMs. METHODS: GOD@POMs were synthesized by a facile one-pot procedure and covalently conjugation. Then, its structure was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). In addition, ultraviolet-visible-near-infrared (UV-vis-NIR) absorption spectrum and infrared thermal camera were applied to evaluate the catalytic and photothermal performance, respectively. Moreover, to confirm the therapeutic effects in vitro, cell counting kit-8 (CCK-8) assay, live/dead staining and ROS staining were performed. Furthermore, the biosafety of GOD@POMs was investigated via blood routine, blood biochemistry and hematoxylin and eosin (H&E) staining in Kunming mice. Besides, the C6 glioma tumor-bearing mice were constructed to evaluate its anti-tumor effects in vivo and its photoacoustic (PA) imaging capability. Notably, RNA sequencing, H&E, TdT-mediated dUTP nick end labeling (TUNEL) and Ki-67 staining were also conducted to disclose its underlying anti-tumor mechanism. RESULTS: In this multifunctional nanosystem, GOD can effectively catalyze the oxidation of intratumoral glucose into gluconic acid and H2O2, achieving the cancer starvation therapy. Meanwhile, the generated gluconic acid decreases the pH in TME resulting in POM aggregation, which enables PA imaging-guided tumor-specific photothermal therapy (PTT), especially in the second near-infrared (NIR-II) biological window. Importantly, the Mo (VI) sites on POM can be reduced to Mo (V) active sites in accompany with GSH depletion, and then the post-produced Mo (V) transforms in situ overproduced H2O2 into singlet oxygen (1O2) via Russell mechanism, achieving self-enhanced CDT. Moreover, the PTT-triggered local tumor temperature elevation augments the synergistic nanocatalytic-therapeutic efficacy. CONCLUSIONS: Consequently, the integration of GOD-induced starvation therapy, H2O2 self-supply/GSH-depletion enhanced Mo-based CDT, and POM aggregation-mediated PTT endow the GOD@POMs with remarkable synergistic anticancer outcomes with neglectable adverse effects.

13.
Bioorg Med Chem ; 73: 117007, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150341

RESUMO

Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC50 value (0.09 µM < IC50 < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC50 = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC50 = 0.73 µM and 0.14 µM respectively), and A549 cells (IC50 = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC50 = 3.1 ± 0.5 µM) than colchicine (IC50 = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network.


Assuntos
Antineoplásicos , Moduladores de Tubulina , Compostos de Anilina/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células , Colchicina/química , Colchicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Piridinas/farmacologia , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologia
14.
Front Oncol ; 12: 985613, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119513

RESUMO

Background: Proline metabolism is closely related to the occurrence and development of cancer. Δ1-Pyrroline-5-carboxylate reductase (PYCR) is the last enzyme in proline biosynthesis. As one of the enzyme types, PYCR1 takes part in the whole process of the growth, invasion, and drug resistance of cancer cells. This study investigated PYCR1 expressions in cancers together with their relationship to clinical prognosis. Methods: A thorough database search was performed in PubMed, EMBASE, and Cochrane Library. RevMan5.3 software was used for the statistical analysis. Results: Eight articles were selected, and 728 cancer patients were enrolled. The cancer types include lung, stomach, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and renal cell carcinoma. The meta-analysis results showed that the expression of PYCR1 was higher in the clinical stage III-IV group than that in the clinical stage I-II group (OR = 1.67, 95%CI: 1.03-2.71), higher in the lymph node metastasis group than in the non-lymph node metastasis group (OR = 1.57, 95%CI: 1.06-2.33), and higher in the distant metastasis group than in the non-distant metastasis group (OR = 3.46, 95%CI: 1.64-7.29). However, there was no statistical difference in PYCR1 expression between different tumor sizes (OR = 1.50, 95%CI: 0.89-2.53) and degrees of differentiation (OR = 0.82, 95%CI: 0.54-1.24). Conclusion: PYCR1 had a high expression in various cancers and was associated with cancer volume and metastasis. The higher the PYCR1 expression was, the poorer the cancer prognosis was. The molecular events and biological processes mediated by PYCR1 might be the underlying mechanisms of metastasis.

15.
Plant Biotechnol J ; 20(7): 1387-1401, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35560858

RESUMO

Amylose content is a crucial physicochemical property responsible for the eating and cooking quality of rice (Oryza sativa L.) grain and is mainly controlled by the Waxy (Wx) gene. Previous studies have identified several Dull genes that modulate the expression of the Wxb allele in japonica rice by affecting the splicing efficiency of the Wxb pre-mRNA. Here, we uncover dual roles for a novel Dull gene in pre-mRNA splicing and microRNA processing. We isolated the dull mutant, du13, with a dull endosperm and low amylose content. Map-based cloning showed that Du13 encodes a C2 H2 zinc-finger protein. Du13 coordinates with the nuclear cap-binding complex to regulate the splicing of Wxb transcripts in rice endosperm. Moreover, Du13 also regulates alternative splicing of other protein-coding transcripts and affects the biogenesis of a subset of microRNAs. Our results reveal an evolutionarily conserved link between pre-mRNA splicing and microRNA biogenesis in rice endosperm. Our findings also provide new insights into the functions of Dull genes in rice and expand our knowledge of microRNA biogenesis in monocots.


Assuntos
MicroRNAs , Oryza , Sintase do Amido , Amilose/metabolismo , Endosperma/genética , Endosperma/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Sintase do Amido/genética , Ceras/metabolismo , Zinco/metabolismo
16.
Ultrason Sonochem ; 86: 106026, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35537315

RESUMO

Nuciferine is an important drug candidate for the treatment of many diseases. However, there is no general method for its low - cost production. In this work, a feasible method for the production of nuciferine from lotus leaf, using ultrasonic-assisted extraction-solid phase extraction (UAE-SPE) as extraction and cleanup procedure, was developed. Petroleum ether and silica gel have been successfully used as extraction solvent and adsorbent to integrate UAE with SPE, respectively. Except for filtration, no treatment (e.g. concentration and redissolution, etc) was needed on UAE extract before SPE and the effluents obtained in the loading process of SPE could be used as UAE extraction solvent without purification. No obvious decline in the extraction efficiency of UAE and adsorption capacity of SPE was observed at least for 5 runs, which provides a feasible way for the continuous production of nuciferine in industry, i.e. Cyclic UAE-SPE. Moreover, SPE column could be conveniently regenerated and reused without significant decline in its adsorption capacity at least for 5 cycles, which can be used to reduce the cost of the whole system further. In comparison with other cleanup procedures, Cyclic UAE-SPE showed apparent advantages in energy conservation and emission reduction. LLE and crystallization were applied to separate nuciferine from other impurities further. Under optimum conditions, the total recovery rate of nuciferine with a purity over 90.0% from lotus leaf reached 50.1%. All in all, the developed method has advantages in convenient operation, low cost, and high efficiency, thus, is fitting for the production of high purity nuciferine.


Assuntos
Aporfinas , Lotus , Aporfinas/análise , Aporfinas/química , Lotus/química , Folhas de Planta/química , Solventes
17.
Materials (Basel) ; 15(5)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35268975

RESUMO

The x-SnO2/α-Fe2O3 (x = 0.04, 0.07, and 0.1) heterogeneous composites were successfully prepared via a two-step solvothermal method. These composites were systematically characterized by the X-ray diffraction technique, field emission scanning electron microscopy, an energy dispersive spectrometer, X-ray photoelectron spectroscopy and a UV-visible spectrometer. It was found that SnO2 nanoparticles were uniformly decorated on the surface of α-Fe2O3 particles in these heterogeneous composites. A comparative study of methylene blue (MB) photodegradation by α-Fe2O3 and x-SnO2/α-Fe2O3 composites was carried out. All x-SnO2/α-Fe2O3 composites showed higher MB photodegradation efficiency than α-Fe2O3. When x = 0.07, the MB photodegradation efficiency can reach 97% in 60 min. Meanwhile, the first-order kinetic studies demonstrated that the optimal rate constant of 0.07-SnO2/α-Fe2O3 composite was 0.0537 min-1, while that of pure α-Fe2O3 was only 0.0191 min-1. The catalytic mechanism of MB photodegradation by SnO2/α-Fe2O3 was examined. The SnO2 can act as a sink and help the effective transfer of photo-generated electrons for decomposing hydrogen peroxide (H2O2) into active radicals. This work can provide a new insight into the catalytic mechanism of the photo-Fenton process.

18.
Sleep Med ; 91: 51-58, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35272117

RESUMO

OBJECTIVE: To perform a systematic review and network meta-analysis to provide comparative evidence and quantitative hierarchies of the effectiveness of positive airway pressure (PAP) treatment on obesity hypoventilation syndrome (OHS). METHODS: We searched PubMed, Embase, and Cochrane Library databases for relevant articles about the treatment of OHS published from the time of database creation to February 2021. Two independent reviewers performed the study search and screening, quality assessment and data extraction. The network meta-analysis within the frequentist framework was performed using Stata 15.0. The outcomes included changes in arterial blood gases, sleep quality, and polysomnography parameters. RESULTS: Ten articles were included in the study. The results of the network meta-analysis showed that PAP treatment could decrease the partial pressure of carbon dioxide, bicarbonate level, apnea-hypopnea index, Epworth sleepiness scale score, and percentage of light sleep, and increase the partial pressure of oxygen, oxygen saturation, and percentage of rapid eye movement sleep and deep sleep when compared with control group in OHS patients. In addition, the results of the derived hierarchy showed that BPAP-AVAPS and BPAP-ST were the first two modes of PAP treatment that reduced the partial pressure of carbon dioxide and percentage of light sleep and improved the percentage of rapid eye movement sleep and deep sleep. However, there was no difference in the quality of life, total sleep time, and sleep efficiency between any mode of PAP treatment and the control group. CONCLUSIONS: PAP treatment is beneficial for OHS patients, and the modes of BPAP-AVAPS and BPAP-ST demonstrated the largest improvement in hypercapnia and objective sleep structure.


Assuntos
Síndrome de Hipoventilação por Obesidade , Dióxido de Carbono , Pressão Positiva Contínua nas Vias Aéreas/métodos , Humanos , Metanálise em Rede , Síndrome de Hipoventilação por Obesidade/terapia , Polissonografia , Qualidade de Vida
19.
Pharmazie ; 77(2): 59-66, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35209965

RESUMO

Background: Patients with prostate cancer often develop resistance to androgen deprivation therapy, a condition called castration-resistant prostate cancer (CRPC). Enzalutamide (MDV3100) can prolong the survival of patients with CRPC after chemotherapy, but ∼50% of patients eventually relapse and develop resistance to MDV3100. Thus, it is necessary to explore new treatment methods to improve the therapeutic effect of MDV3100. Tyrosine kinases play an essential role in the pathogenesis of CRPC. Methods: MTT assay was used to detect the inhibitory effects of MDV3100 and tyrosine kinase inhibitor on prostate cancer cells. CompuSyn version 1.0 was used to calculate the combination index (CI) values using the Chou-Talalay method. Clone formation and EdU assay were used to detect the effect of afatinib combined with MDV3100 on the proliferation of 22Rv1 cells. RT-qPCR and Western blot were used to explore the mechanism of drug combination. The aim of the present study was to determine the effects of several tyrosine kinase inhibitors (TKIs) when used in combination with MDV3100 in vitro. Results: The results demonstrated that TKIs combined with MDV3100 exerted a synergistic effect on a variety of PCa cells. Afatinib combined with MDV3100 could suppress the proliferation and migration of 22RV1 cells, as well as cause their cell cycle arrest and apoptosis. Mechanistically, afatinib effectively reduced the protein expression levels of HER2 and HER3 and inhibited EGFR phosphorylation, thereby enhancing the effect of MDV3100 and suppressing CRPC. Conclusions: These findings suggested that afatinib treatment improved the effect of MDV3100 on 22RV1 cells, highlighting this drug as a potential therapeutic strategy for patients with CRPC.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Afatinib/farmacologia , Afatinib/uso terapêutico , Antagonistas de Androgênios , Benzamidas , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Recidiva Local de Neoplasia , Nitrilas/farmacologia , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/metabolismo , Receptores Androgênicos/uso terapêutico
20.
Sleep Breath ; 26(2): 689-696, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34302610

RESUMO

PURPOSE: Ultra-wideband bio-radar (UWB) is a new non-contact technology that can be used to screen for obstructive sleep apnea (OSA). However, little information is available regarding its reliability. This study aimed to evaluate the effectiveness of UWB and to determine if UWB could provide a novel and reliable method for the primary screening of sleep-related breathing disorders. METHOD: Subjects with suspected OSA from the sleep center of the First Hospital of the China Medical University were assessed over the period of September 2018 to April 2019 for enrollment in the study. Three detection methods were simultaneously used, including the STOP-Bang questionnaire (SBQ), UWB, and standard polysomnography (PSG). The data were analyzed using a fourfold table, receiver operating characteristic curves, Spearman rank correlation coefficients, Bland-Altman plots, and epoch-by-epoch analysis. RESULT: Of 67 patients, 56 were men, mean age was 43 ± 11 years, mean body mass index was 27.8 ± 4.8 kg/m2, and mean SBQ score was 4.8 ± 1.6. The apnea-hypopnea index (AHI) (r = 0.82, p < 0.01) and minimum arterial oxygen saturation (r = 0.80, p < 0.01) of the UWB were positively correlated with those obtained from the PSG. UWB performed better than SBQ, as indicated by the larger area under the curve (0.85 vs. 0.632). The sensitivity and specificity of the UWB-AHI were good (100%, 70%, respectively). CONCLUSIONS: UWB performs well in the screening of OSA and can provide reliable outcomes for the screening of OSA at the primary level.


Assuntos
Radar , Apneia Obstrutiva do Sono , Adulto , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Polissonografia , Reprodutibilidade dos Testes , Sono , Apneia Obstrutiva do Sono/diagnóstico , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA