Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
1.
J Int Med Res ; 52(5): 3000605241252238, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38759222

RESUMO

An accessory cavitated uterine mass (ACUM) is a very rare obstructive genital malformation characterized by pelvic pain and severe dysmenorrhea. It is easily mistaken for other obstructive genital malformations in women, such as cystic uterine adenomyosis or cystic degeneration of uterine fibroids. This case report describes a 30-year-old patient with a huge uterine cornual mass. Successful resection was performed by surgical excision, and the lesion was diagnosed as an ACUM. Given the rarity of a giant ACUM, this report also includes a brief review of the relevant literature.


Assuntos
Útero , Humanos , Feminino , Adulto , Útero/anormalidades , Útero/cirurgia , Útero/patologia , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/patologia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Resultado do Tratamento , Dismenorreia/etiologia , Dismenorreia/cirurgia , Dismenorreia/diagnóstico
2.
Exp Biol Med (Maywood) ; 249: 10108, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510490

RESUMO

Acute myeloid leukemia (AML) is one of the most threatening hematological malignances. cGAS-STING pathway plays an important role in tumor immunity and development. However, the prognostic role of cGAS-STING pathway in AML remains unknown. Firstly, The expression of cGAS and STING was analyzed by bioinformatics analysis. Subsequently, Bone marrow samples were collected from 120 AML patients and 15 healthy individuals in an independent cohort. The cGAS and STING expression was significantly elevated in AML patients compared with healthy controls. Patients with high cGAS and STING expression had a higher NRAS/KRAS mutation rate and lower complete remission (CR) rate. High cGAS and STING expression was significantly associated with lower overall survival (OS) and disease-free survival (DFS). Our findings revealed that the expression levels of cGAS and STING in AML are elevated. High expression of cGAS and STING correlated with worse OS and DFS and may be a useful biomarker for inferior prognosis in AML patients.


Assuntos
Leucemia Mieloide Aguda , Humanos , Prognóstico , Leucemia Mieloide Aguda/metabolismo , Intervalo Livre de Doença , Expressão Gênica
3.
J Colloid Interface Sci ; 663: 1005-1018, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38452542

RESUMO

The creation of a Z-scheme heterojunction is a sophisticated strategy to enhance photocatalytic efficiency. In our study, we synthesized an In2S3/MnO2/BiOCl dual Z-scheme heterostructure by growing BiOCl nanoplates on the sheets of In2S3 nanoflowers, situated on the surface of MnO2 nanowires. This synthesis involved a combination of hydrothermal and solution combustion methods. Experiments and density functional theory (DFT) calculations demonstrated that the In2S3/MnO2/BiOCl composite exhibited notable photo reduction performance and photocatalytic stability. This was attributed to the pivotal roles of BiOCl and MnO2 in the composite, acting as auxiliaries to enhance the electronic structure and facilitate the adsorption/activation capacity of CO2 and H2O. The yield rates of CO, CH4, and C2H4 over In2S3/MnO2/BiOCl as the catalyst were 3.94, 5.5, and 3.64 times higher than those of pure In2S3, respectively. Photoelectrochemical analysis revealed that the dual Z-scheme heterostructure, with its oxygen vacancies and large surface area, enhanced CO2 absorption and active sites on the nanoflower/nanowire intersurfaces. Consequently, the dual Z-scheme charge transfer pathway provided efficient channels for boosting electron transfer and charge separation, resulting in high C2H4, CH4, and CO yields of formed and exihibits an promising photoreduction rate of CO2 to CO (51.2 µmol/g.h), CH4 (42.4 µmol/g.h) and C2H4 (63.2 µmol/g.h), respectively. DFT, in situ Diffuse reflectance infrared fourier transform spectroscopy, and temperature-programmed desorption tests were employed to verify the intermediates pathway. The study proposed a potential photocatalytic mechanism based on these findings.

4.
J Colloid Interface Sci ; 661: 544-563, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38308894

RESUMO

The realization of 2D/2D Van der Waals (VDW) heterojunctions represents an advanced approach to achieving superior photocatalytic efficiency. However, electron transfer through Van der Waals heterojunctions formed via ex-situ assembly encounters significant challenges at the interface due to contrasting morphologies and potential barriers among the nanocomposite substituents. Herein, a novel approach is presented, involving the insertion of a phosphate group between copper phthalocyanine (CuPc) and B-doped and N-deficient g-C3N4 (BDCNN), to design and construct a Van der Waals heterojunction labeled as xCu[acs]/yP-BDCNN. The introduction of phosphate as a charge modulator and efficient conduit for charge transfer within the heterojunction resulted in the elimination of spatial barriers and induced electron movement from BDCNN to CuPc in the excited states. Consequently, the catalytic central Cu2+ in CuPc captured the photoelectrons, leading to the conversion of CO2 to C2H4, CO and CH4. Remarkably, this approach resulted in a 78-fold enhancement in photocatalytic efficiency compared to pure BDCNN. Moreover the findings confirm that the 2D-2D 4Cu[acs]/9P-BDCNN sheet-like heterojunction effectively boosts photocatalytic activity for persistent pollutants such as methyl orange (MO), methylene blue (MB), rhodamine B (RhB), and tetracycline antibiotics (TCs). The introduction of "interfacial interacting" substances to establish an electron transfer pathway presents a novel and effective strategy for designing photocatalysts capable of efficiently reducing CO2 into valuable products.

5.
Langmuir ; 40(5): 2729-2744, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38277675

RESUMO

We synthesized Sr-doped spinel CoCr2O4 using the solution combustion method and characterized the structure, morphology, chemical state, and photocatalytic properties through different techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and electrochemical impedance spectroscopy (EIS). 30-50 nm cuboid CoCr2O4 nanocrystals with Sr doping levels ranging from 0 to 0.6% were obtained; the increasing Sr doping deformed the coordination number of Co and Cr, transitioning to octahedral and tetrahedral units, inducing the phase transition from spinel to inverse spinel at 0.6% Sr content. This modification enhanced optical absorption, reduced the energy band gap, increased photoluminescence intensity, and maintained a high-spin state with oxygen vacancies. 0.6% Sr-doped CoCr2O4 demonstrated the highest photocatalytic efficiency at 93%. The XRD structure and photocatalytic activity remained at 87% over 7 cycles after 14 h. Employing degradation pathways and Mott-Schottky curves elucidated the enhancement mechanism.

6.
Death Stud ; 48(4): 417-426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37416944

RESUMO

Death attitudes can have significant impacts on individuals' mental health. The present study used a person-centered approach to identify 588 Chinese college students' profiles of death attitudes (i.e., fear of death, death avoidance, neutral acceptance, escape acceptance, and approach acceptance), as well as their associations with socio-demographic factors and mental health outcomes. Latent profile analysis identified five subgroups of students: healthy (28.8%), acceptant (11.7%), indifferent (43.5%), paradoxical (10.7%), and avoidant (5.3%). The healthy profile had the most favorable mental health outcomes, whereas the paradoxical profile had the least favorable mental health outcomes. Moreover, women and students from better-resourced universities were more likely to report adaptive patterns of death attitudes. Our findings demonstrated the advantages of using a person-centered approach to achieve a more nuanced understanding of Chinese college students' death attitudes in relation to their mental health. The findings can inform death-related education and mental health interventions for college students.


Assuntos
Medo , Saúde Mental , Humanos , Feminino , Estudantes/psicologia , Universidades
7.
Heliyon ; 9(7): e17709, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37483723

RESUMO

Exploratory innovation is critical to the breakthrough of core technologies in the integrated circuit (IC) industry, and cooperative innovation is a promising form of IC industry development. According to the viewpoint of social network, this paper constructs intercity networks of the IC industry by using a data set of cooperation patents from 2011 to 2020 in China. We uncover the evolution characteristics of the innovation networks, explore the relationship between network centrality and exploratory innovation in a city, and consider universities and development zones, named support organizations, as moderating variables. The results of the social network analysis (SNA) and dynamic panel system generalized method of moments model (System-GMM) are given as follows: Cities are increasingly inclined to collaborate with counterparts over time for innovation, but the overall network scale remains small. Beijing occupies core position in the networks. A cooperative innovation model driven by peripheral cities has been formed as the number of the peripheral cities has gradually increased. The network centrality of a city has a positive effect on its exploratory innovation. Both universities and development zones positively moderate the effect of network centrality on exploratory innovation. Based on the characteristics of the network, our study reveals the importance of taking the internal structure of the network and the node support environment into the same framework, which provides guidance for the innovative development of the world IC industry.

8.
Biochem Biophys Res Commun ; 671: 278-285, 2023 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-37311265

RESUMO

INTRODUCTION: Gestational diabetes mellitus (GDM) is the first occurrence of diabetes due to abnormal maternal sugar metabolism after pregnancy, which may lead to adverse pregnancy outcomes. Hesperidin is known to decrease in the cord blood of GDM with obesity, but its role is unknown. This study aims to explore the potential function of hesperidin in GDM with obesity to develop new therapeutic ideas. METHODS: Peripheral blood and placental tissues from GDM and GDM with obesity patients were collected to isolate human villous trophoblasts and detection. Bioinformatics was used to analyze the differential methylation genes between GDM and GDM with obesity. Immunofluorescence was applied for the detection of CK7 expression. Cells vitality was detected by CCK8 and transwell. Molecular docking was applied to predict the binding of hesperidin and ATG7 protein. Inflammation and m6A levels was analyzed by ELISA. ATG7, LC3, TLR4 and P62 proteins was analyzed by Western blot. RESULTS: The methylation of ATG7 gene was up-regulated in GDM with obesity compared with GDM. The m6A and autophagy proteins levels in GDM with obesity were higher than that in GDM. LPS with 2.5-25 mM glucose induced the increase of autophagy proteins, inflammation and m6A levels in human villous trophoblasts. Hesperidin formed hydrogen bonds and hydrophobic interactions with ATG7 proteins. Hesperidin (0.25 µM) inhibited the autophagy proteins and m6A level in LPS and 25 mM glucose-induced human villous trophoblasts. DISCUSSION: GDM with obesity followed the increase of autophagy proteins and m6A levels. Hesperidin inhibited the autophagy proteins and m6A level in LPS and glucose-induced human villous trophoblasts.


Assuntos
Diabetes Gestacional , Hesperidina , Gravidez , Humanos , Feminino , Placenta/metabolismo , Trofoblastos/metabolismo , Hesperidina/farmacologia , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Metilação , Simulação de Acoplamento Molecular , Diabetes Gestacional/metabolismo , Obesidade/metabolismo , Inflamação/metabolismo , Autofagia , Glucose/farmacologia , Glucose/metabolismo
9.
Front Genet ; 14: 1068923, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36845397

RESUMO

GATA1 is required for normal erythropoiesis. Exonic/intronic GATA1 mutations causes Diamond-Blackfan Anemia (DBA)-like disease. Herein, we present a case of a 5-year-old boy with anemia of unknown etiology. Whole-exome sequencing revealed a de novo GATA1 c.220 + 1G>C mutation. The reporter gene assay revealed that such mutations did not affect on GATA1 transcriptional activity. The normal transcription of GATA1 was disturbed, as evidenced by increased expression of the shorter GATA1 isoform. RDDS prediction analysis revealed that abnormal GATA1 splicing might be the underlying mechanism disrupting GATA1 transcription, thereby impairing erythropoiesis. Prednisone treatment significantly improved erythropoiesis, evidenced by increased hemoglobin and reticulocyte counts.

10.
Langmuir ; 38(50): 15579-15591, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36473723

RESUMO

There has been a dire need for the exploration of renewable clean hydrogen energy recourses in recent years. In this work, we investigated the photocatalytic hydrogen production of heterostructured Ti3C2/TiO2/rGO composites. Ti3C2/TiO2/rGO heterojunction nanocomposites were synthesized using two-step calcination and hydrothermal methods, and the optimum in situ growth ratio of TiO2 of 71.8% (nTi-O/nTi) and rGO mass ratio (mRGO/mTiO2/mTi3C2) of 12% were obtained. The target photocatalyst presented an outperforming photocatalytic hydrogen production performance of 1671.85 µmol·g-1 hydrogen production capacity in 4 h, with the maximum hydrogen production rate of 808.11 µmol·g-1·h-1 in the first hour being 3.08 times the maximum hydrogen production rate of bare TiO2 (262.66 µmol·g-1·h-1). The excellent hydrogen production performance was due to the formed rutile TiO2 and the constructed heterojunction of Ti3C2/TiO2/rGO, where rGO provided different electron transport channels, and made charge transfer easier, and restrained the recombination efficiency of electrons and holes.

11.
Pharmaceuticals (Basel) ; 15(11)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36355485

RESUMO

Leukemia stem cells (LSCs) constitute the critical barrier to the cure of acute myeloid leukemia (AML) due to their chemoresistance and immune evasion property. Herein, the role of anlotinib, a multiple tyrosine kinase inhibitor, in killing LSCs and regulating chemoresistance and immune evasion was explored. Anlotinib treatment induced apoptosis of LSC-like cells as well as primary AML LSCs, while sparing the normal mononuclear cells in vitro. Moreover, anlotinib could impair the regeneration capacity of LSCs in the patient-derived leukemia xenograft mouse model. Mechanistically, anlotinib inhibited phosphorylation of c-kit, JAK2/STAT3, and STAT5, and downregulated STAT3 and STAT5 expression. In addition, anlotinib downregulated the anti-apoptotic proteins Bcl-2 and Bcl-xL, and upregulated Bax, thereby enhancing the sensitivity of LSCs to idarubicin in vitro. Intriguingly, anlotinib could also partially rescue the interferon-g production of T cells cocultured with LSCs by downregulating PD-L1 expression. In conclusion, anlotinib showed anti-LSC activity and the potential to enhance the sensitivity to idarubicin and inhibit the immunosuppressive feature of LSCs via JAK2/STAT signaling pathway downregulation in the preclinical study. Our results provided a rational basis for combinatory strategies involving anlotinib and chemotherapy or immunotherapy.

12.
Cardiovasc Diabetol ; 21(1): 237, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348348

RESUMO

BACKGROUND: Optimal treatment strategies for patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. The goal of this study was to compare the treatment effects of different therapeutic agents for patients with HFpEF. METHODS: Randomized controlled trials (RCTs) published before June 2022 were searched from PubMed, Clinical Trials gov, and the Cochrane Central Register databases. Combined odds ratios (ORs) with 95% confidence intervals (CI) were calculated for the primary and secondary outcomes. All-cause death was the primary endpoint and cardiac death, hospitalization for HF, and worsening HF (WHF) events were secondary endpoints in this meta-analysis. RESULTS: Fifteen RCTs including 31,608 patients were included in this meta-analysis. All-cause and cardiac death were not significantly correlated between drug treatments and placebo. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduced HF hospitalizations [odds ratio (OR) = 0.64, (95% confidence interval (95%CI 0.43 - 0.96), OR = 0.73, (95%CI 0.61 - 0.86), and OR = 0.74, (95%CI 0.66 - 0.83), respectively] without heterogeneity among studies. Only SGLT2 inhibitors significantly reduced WHF events [OR = 0.75, (95%CI 0.67 - 0.83)]. CONCLUSIONS: No treatments were effective in reducing mortality, but ARNIs, ACEIs or SGLT2 inhibitors reduced HF hospitalizations and only SGLT2 inhibitors reduced WHF events for patients with HFpEF.


Assuntos
Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Volume Sistólico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/induzido quimicamente , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Morte
13.
Front Pharmacol ; 13: 992376, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249742

RESUMO

Aimed to evaluate and compare the interactive effects of different antiplatelet or anticoagulation strategies in patients with chronic coronary syndromes (CCS) after percutaneous coronary intervention (PCI). Randomized controlled trials comparing different antiplatelet or anticoagulant strategies in patients with CCS after PCI were included. The primary outcomes were major adverse cardiovascular event (MACE), mortality, ischemic and bleeding events. Compared to aspirin alone, addition of prasugrel or ticagrelor to aspirin resulted in lower risk of myocardial infarction (MI) [odds ratio (OR): 0.38 (95% confidence interval 0.38-0.62); 0.810-0.84 (0.69-0.98)] and any stroke [0.56 (0.42-0.75)] at the expense of increased risk of major bleeding [1.79 (1.34-2.39); 2.08-2.38 (1.56-3.28)], whereas, clopidogrel monotherapy reduced the risk of any stroke, major bleeding, and intracranial bleeding. On subgroup analysis, compared with aspirin alone, addition of prasugrel resulted in lower MACE [0.72 (0.60-0.86)], MI [0.48 (0.38-0.62)], and stent thrombosis [0.29 (0.09-0.91)], whereas, addition of rivaroxaban 2.5 mg resulted in lower risk of MACE [0.72 (0.60-0.87)], cardiac death [0.71 (0.52-0.98)] and any stroke [0.65 (0.45-0.95)], but not reduced MI. Both prasugrel and rivaroxaban 2.5 mg increased major bleeding [1.79 (1.34-2.39); 1.72 (1.33-2.22)]. Clopidogrel monotherapy was associated with lower MACE [0.72 (0.58-0.90)], any stroke [0.42 (0.24-0.73)], and major bleeding [0.62 (0.40-0.96)]. Adding prasugrel or ticagrelor led to a reduced incidence of MI and prasugrel was also found to reduce the risk of MACE and stent thrombosis in CCS patients with low risk of bleeding after PCI. Clopidogrel monotherapy has advantage in reducing MACE, stroke, and major bleeding events in CCS patients at high risk of bleeding after PCI. Systematic Review Registration: https://clinicaltrials.gov/, PROSPERO Identifier: CRD 42021291050.

14.
PLoS One ; 17(9): e0272026, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36149853

RESUMO

Based on the modified gravity model, a spatial correlation network of innovation was constructed among cities in Guangdong, China. Social network analysis was employed to explore their evolution characteristics during 2009-2017. The results indicate that the innovation output of prefecture-level cities in Guangdong Province shows both spatial correlations and differences. Their network shows lower density, higher efficiency, and rigid stratification properties. Based on small cluster analysis, these cities are classified into four blocks, the members of which changed. In 2017, four well-defined subgroups formed, which are "bidirectional spillover plate", "main spillover plate", "net beneficial plate", and "agent plate". With this network, the geographical characteristics of the innovation capabilities and differences among the cities in Guangdong, as well as the different positions and roles of each city in the associated network, can be properly understood. Consequently, the transmission mechanisms and development strategies of innovation in Guangdong Province can be better explored.


Assuntos
Desenvolvimento Econômico , China , Cidades
15.
J Obstet Gynaecol Res ; 48(11): 2798-2806, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36055678

RESUMO

AIM: To validate risk factors and a nomogram prediction model for the failure of a trial of labor after cesarean section (TOLAC) in a Chinese population. METHODS: We included women who tried TOLAC between January 2017 and May 2019, grouped according to the success/failure of TOLAC. The patients were randomized 3:1 into the development and validation sets. Multivariable logistic regression analyses were used to develop a nomogram prediction model for TOLAC failure. RESULTS: In total, 535 (86.3%) of the women (n = 620) aged 29-34 years had a successful vaginal birth after cesarean (VBAC). All women had a fully healed previous uterine incision. The univariable analyses showed that the cephalopelvic score (p < 0.001), BMI (p = 0.001), full engagement into the pelvis (p < 0.001), Bishop cervical maturity score (p < 0.001), and estimated fetal weight at admission (p < 0.001) could enter the multivariable model. Furthermore, the multivariable analysis showed that the cephalopelvic score (OR = 0.42, 95%CI: 0.23-0.77, p = 0.005), full engagement in the pelvis (OR = 0.16, 95%CI: 0.08-0.33, p < 0.001), and Bishop cervical maturity score (OR = 0.46, 95%CI: 0.35-0.59, p < 0.001) were independent predictors of the failure of TOLAC. CONCLUSION: This study proposes a nomogram that can assess the risk of failure of TOLAC in Chinese pregnant women. The statistical model could help clinicians know the likelihood of successful TOLAC in the clinical setting.


Assuntos
Prova de Trabalho de Parto , Nascimento Vaginal Após Cesárea , Feminino , Gravidez , Humanos , Cesárea , Estudos Retrospectivos , Nomogramas , Nascimento Vaginal Após Cesárea/efeitos adversos
16.
Biosci Biotechnol Biochem ; 86(12): 1631-1640, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36107816

RESUMO

Angiopoietin-like protein 2 (ANGPTL2) plays versatile roles in various cardiovascular diseases. Its connection to doxorubicin (DOX)-related cardiomyopathy, however, remains elusive. To determine the role of ANGPTL2, an adeno-associated viral vector was used to overexpress ANGPTL2 in the murine heart 4 weeks before DOX treatment (15 mg/kg). Moreover, mice were injected with adenoviral vectors to knock down ANGPTL2 in the myocardium. Echocardiography and hemodynamics were used to determine the cardiac function. The effect of ANGPTL2 and its downstream target were elucidated by applying molecular and biochemical strategies. We found that ANGPTL2 expression was significantly increased in response to DOX stimulation. Moreover, cardiac-specific ANGPTL2 overexpression exacerbated DOX-related cardiac dysfunction, myocardial apoptosis, and oxidative stress. Mechanistically, ANGPTL2 aggravated DOX-induced cardiac injury via inhibiting the dual specificity phosphatase 1 (DUSP1) pathway and DUSP1 overexpression significantly impeded DOX-induced cardiomyopathy in ANGPTL2-overexpressed mice. Altogether, ANGPTL2 aggravated DOX-related cardiac injury by suppressing the DUSP1 pathway.


Assuntos
Cardiomiopatias , Cardiotoxicidade , Animais , Camundongos , Proteínas Semelhantes a Angiopoietina/genética , Proteínas Semelhantes a Angiopoietina/metabolismo , Apoptose , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiotoxicidade/metabolismo , Doxorrubicina/toxicidade , Fosfatase 1 de Especificidade Dupla/genética , Fosfatase 1 de Especificidade Dupla/metabolismo , Fosfatase 1 de Especificidade Dupla/farmacologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo
17.
Transl Oncol ; 25: 101516, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35985203

RESUMO

OBJECTIVES: Despite advances in the development of novel targeted therapies, the need for B-ALL alternative treatments has not been met. Anlotinib could blunt the proangiogenic activity of VEGFR, PDGFR, and FGFR, and has shown strong antitumor activities across multiple tumors. However, anlotinib cytotoxicity against B-ALL has not ever been evaluated, thus prompting us to initiate this study. METHODS: Expression2Kinases program was used to identify potential treatment targets. Cell viability and apoptosis were determined by CCK-8 and Annexin V/PI staining kit, respectively. qRT-PCR and Western blotting were utilized to investigate the molecular mechanisms. In vivo antileukemia activity of Anlotinib was evaluated in a Ph+ B-ALL patient-Derived Xenograft (PDX) model. RESULTS: Compared with treatment-naive B-ALL cases, RR B-ALL patients had higher activities in the VEGF/VEGFR signaling and the PI3K/AKT/mTOR pathway. Exposure of Ph- and Ph+ B-ALL cells to anlotinib resulted in significant cell viability reduction, apoptosis enhancement, and cell cycle arrest at G2/M phase. Importantly, anlotinib treatment led to remarkably decreased leukemia burdens and extended the survival period in a Ph+ B-ALL PDX model. Blockade of the role of the proangiogenic mediators, comprising VEGFR2, PDGFR-beta, and FGFR3, played a critical role in the cytotoxicity of anlotinib against Ph- and Ph+ B-ALL. Moreover, anlotinib dampened the activity of PI3K/AKT/mTOR pathway that resides in the convergence of the three mentioned proangiogenic signals. CONCLUSION: This work provides impressive preclinical evidence of anlotinib against Ph- and Ph+ B-ALL and raises a rationale for future clinical evaluation of this drug in the management of Ph- and Ph+ B-ALL.

18.
Front Psychiatry ; 13: 880496, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693956

RESUMO

Objectives: Although several studies have reviewed the suicidal risk of antidepressants, the conclusions remain inconsistent. We, therefore, performed a meta-analysis of observational studies to address the association between exposure to antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and the risk of suicide and suicide attempt in children and adolescents. Methods: MEDLINE and Embase were searched from January 1990 to April 2021. Seventeen cohort and case-control studies were identified that reported suicide or suicide attempt in children and young adults (aged 5-25 years) who were exposed to any antidepressants. We extracted the estimates and corresponding 95% confidence intervals (CIs) from each publication. Results: The results showed that antidepressant exposure significantly increased the risk of suicide and suicide attempt when compared with no antidepressant usage among children and adolescents. The pooled relative risk (RR) was 1.38 (95% CI: 1.16-1.64; I 2 = 83.1%). Among the antidepressants, SSRI use was associated with an increased risk of suicide and suicide attempt, and the pooled RR was 1.28 (95% CI: 1.09-1.51; I 2 = 68.8%). In subgroup analysis, the attempted suicidal risk of antidepressant and SSRI was significantly increased (RR = 1.35, 95% CI: 1.13-1.61; I 2 = 86.2% for all antidepressants; and RR = 1.26, 95% CI: 1.06-1.48; I 2 = 73.8% for SSRIs), while the completed suicidal risk of antidepressant and SSRI was not statistically significant (RR = 2.32, 95% CI: 0.82-6.53; I 2 = 6.28% for all antidepressants; and RR = 1.88, 95% CI: 0.74-4.79; I 2 = 52.0% for SSRIs). In addition, the risk of suicide and suicide attempt between SSRIs and other antidepressants was similar (RR 1.13, 95% CI: 0.87-1.46, I 2 = 32.4%). Conclusion: The main findings of this meta-analysis provide some evidence that antidepressant exposure seems to have an increased suicidal risk among children and young adults. Since untreated depression remains one of the largest risk factors for suicide and the efficacy of antidepressants is proven, clinicians should evaluate carefully their patients and be cautious with patients at risk to have treatment emergence or worsening of suicidal ideation (TESI/TWOSI) when prescribing antidepressants to children and young patients.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35600958

RESUMO

Background: Gestational diabetes mellitus (GDM) is a common metabolic disorder in pregnancy. The incidence rate is increasing year by year, which seriously threatens the safety of maternal and infant. Obesity is a vital factor in inducing GDM. Pregnant women with GDM account for a large proportion of overweight and obese pregnant women. Our study aimed to explore the potential mechanism of differential metabolites on inflammation and find the intervention and management methods for GDM in overweight and obese pregnant women. Methods: Umbilical cord blood samples and placenta were collected from normal weight pregnant women with GDM (control group) and overweight and obese pregnant women with GDM (obesity group) for a comparative study. Serum inflammatory factors IL-10, TNF-α, IL-6, lipopolysaccharide (LPS), and TLR4 expression were detected by ELISA. The expression levels of BCL-2 and caspase-3 were measured by Western blot. TUNEL staining was used to observe the apoptosis of placental villi. KEGG combined with metabolomics was used to compare the differences of metabolic maps between the two groups. Results: Compared with the control group, the level of anti-inflammatory factor IL-10 in the cord blood was decreased in the obesity group, while the levels of proinflammatory factors TNF-α, IL-6, and LPS were increased. In the placental tissues, the obesity group had higher concentrations of LPS, TLR4, and caspase-3 and lower concentration of BCL-2. Placental villi in the obesity group were more likely to undergo apoptosis than the control group. Correlation analysis showed that the above metabolite concentrations were negatively correlated with TNF-α or LPS. Conclusion: Metabolites could control obesity in the process of controlling the occurrence and development of inflammation.

20.
Front Plant Sci ; 13: 865848, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548314

RESUMO

Recently developed base editors provide a powerful tool for plant research and crop improvement. Although a number of different deaminases and Cas proteins have been used to improve base editors the editing efficiency, and editing window are still not optimal. Fusion of a non-sequence-specific single-stranded DNA-binding domain (DBD) from the human Rad51 protein between Cas9 nickase and the deaminase has been reported to dramatically increase the editing efficiency and expand the editing window of base editors in the mammalian cell lines and mouse embryos. We report the use of this strategy in rice, by fusing a rice codon-optimized human Rad51 DBD to the cytidine base editors AncBE4max, AncBE4max-NG, and evoFERNY. Our results show that the addition of Rad51 DBD did not increase editing efficiency in the major editing window but the editing range was expanded in all the three systems. Replacing the human Rad51 DBD with the rice Rad51 DBD homolog also expanded the editing window effectively.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...