Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 669
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
J Biol Chem ; 300(6): 107309, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38657867

RESUMO

Novel components in the noncanonical Hippo pathway that mediate the growth, metastasis, and drug resistance of breast cancer (BC) cells need to be identified. Here, we showed that expression of SAM and SH3 domain-containing protein 1 (SASH1) is negatively correlated with expression of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) in a subpopulation of patients with luminal-subtype BC. Downregulated SASH1 and upregulated MAP4K4 synergistically regulated the proliferation, migration, and invasion of luminal-subtype BC cells. The expression of LATS2, SASH1, and YAP1 and the phosphorylation of YAP1 were negatively regulated by MAP4K4, and LATS2 then phosphorylated SASH1 to form a novel MAP4K4-LATS2-SASH1-YAP1 cascade. Dephosphorylation of Yes1 associated transcriptional regulator (YAP1), YAP1/TAZ nuclear translocation, and downstream transcriptional regulation of YAP1 were promoted by the combined effects of ectopic MAP4K4 expression and SASH1 silencing. Targeted inhibition of MAP4K4 blocked proliferation, cell migration, and ER signaling both in vitro and in vivo. Our findings reveal a novel MAP4K4-LATS2-SASH1-YAP1 phosphorylation cascade, a noncanonical Hippo pathway that mediates ER signaling, tumorigenesis, and metastasis in breast cancer. Targeted intervention with this noncanonical Hippo pathway may constitute a novel alternative therapeutic approach for endocrine-resistant BC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Neoplasias da Mama , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Serina-Treonina Quinases , Fatores de Transcrição , Proteínas Supressoras de Tumor , Proteínas de Sinalização YAP , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Animais , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Camundongos , Transdução de Sinais , Metástase Neoplásica , Movimento Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Fosforilação , Camundongos Nus , Carcinogênese/genética , Carcinogênese/metabolismo
2.
J Med Virol ; 96(5): e29650, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38727133

RESUMO

To analyze the epidemiological characteristics of group A rotavirus (RVA) diarrhea in Beijing between 2019 and 2022 and evaluate the effectiveness of the RV5 vaccine. Stool specimens were collected from patients with acute diarrhea, and RVA was detected and genotyped. The whole genome of RVA was sequenced by fragment amplification and Sanger sequencing. Phylogenetic trees were constructed using Bayesian and maximum likelihood methods. Descriptive epidemiological methods were used to analyze the characteristics of RVA diarrhea. Test-negative design was used to evaluate the vaccine effectiveness (VE) of the RV5. Compared with 2011-2018, RVA-positive rates in patients with acute diarrhea under 5 years of age and adults decreased significantly between 2019 and 2022, to 9.45% (249/634) and 3.66% (220/6016), respectively. The predominant genotype of RVA had changed from G9-VIP[8]-III between 2019 and 2021 to G8-VP[8]-III in 2022, and P[8] sequences from G8-VP[8]-III strains formed a new branch called P[8]-IIIb. The complete genotype of G8-VP[8]-III was G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. The VE of 3 doses of RV5 was 90.4% (95% CI: 28.8%-98.7%) against RVA diarrhea. The prevalence of RVA decreased in Beijing between 2019 and 2022, and the predominant genotype changed to G8P[8], which may be related to RV5 vaccination. Continuous surveillance is necessary to evaluate vaccine effectiveness and improve vaccine design.


Assuntos
Diarreia , Fezes , Genótipo , Filogenia , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Humanos , Rotavirus/genética , Rotavirus/classificação , Rotavirus/imunologia , Rotavirus/isolamento & purificação , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Infecções por Rotavirus/prevenção & controle , Diarreia/virologia , Diarreia/epidemiologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/imunologia , Pré-Escolar , Prevalência , Pequim/epidemiologia , Masculino , Lactente , Feminino , Adulto , Fezes/virologia , Pessoa de Meia-Idade , Criança , Adulto Jovem , Adolescente , Eficácia de Vacinas , Idoso , Genoma Viral , Recém-Nascido
3.
J Med Virol ; 96(7): e29796, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38982764

RESUMO

Coxsackievirus A16 (CV-A16) is a significant etiologic agent of hand, foot, and mouth disease (HFMD) and herpangina (HA), with the capacity to progress to severe complications, including encephalitis, aseptic meningitis, acute flaccid paralysis, myocarditis, and other critical conditions. Beijing's epidemiological surveillance system, established in 2008, encompasses 29 hospitals and 16 district disease control centers. From 2019 to 2021, the circulation of CV-A16 was characterized by the co-circulation of B1a and B1b clades. Multiple cases of HFMD linked to clade B1c has not been reported in Beijing until 2022. This study enrolled 400 HFMD and 493 HA cases. Employing real-time RT-PCR, 368 enterovirus-positive cases were identified, with 180 selected for sequencing. CV-A16 was detected in 18.89% (34/180) of the cases, second only to CV-A6, identified in 63.33% (114/180). Full-length VP1 gene sequences were successfully amplified and sequenced in 22 cases, revealing the presence of clades B1a, B1b, and B1c in 14, 3, and 5 cases, respectively. A cluster of five B1c clade cases occurred between June 29 and July 17, 2022, within a 7-km diameter region in Shunyi District. Phylogenetic analysis of five complete VP1 gene sequences and two full-genome sequences revealed close clustering with the 2018 Indian strain (GenBank accession: MH780757.1) within the B1c India branch, with NCBI BLAST results showing over 98% similarity. Comparative sequence analysis identified three unique amino acid variations (P3S, V25A, and I235V). The 2022 Shunyi District HFMD cases represent the first instances of spatiotemporally correlated CV-A16 B1c clade infections in Beijing, underscoring the necessity for heightened surveillance of B1c clade CV-A16 in HFMD and HA in this region.


Assuntos
Doença de Mão, Pé e Boca , Filogenia , Humanos , Pequim/epidemiologia , Doença de Mão, Pé e Boca/virologia , Doença de Mão, Pé e Boca/epidemiologia , Masculino , Feminino , Pré-Escolar , Lactente , Criança , Genótipo , Enterovirus/genética , Enterovirus/classificação , Enterovirus/isolamento & purificação , Proteínas do Capsídeo/genética , Adolescente , Monitoramento Epidemiológico
4.
Toxicol Appl Pharmacol ; 489: 117006, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38880189

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal cancers worldwide. Most ESCC patients are diagnosed at an advanced stage; however, current research on in vivo animal models accurately reflecting their clinical presentation is lacking. Alcohol consumption is a major risk factor for ESCC and has been used in several disease models for disease induction. In this study, we used 4-nitroquinoline-1-oxide in combination with ethanol to induce an in vivo ESCC mouse model. Esophageal tissues were stained with hematoxylin and eosin for histopathological examination and lesion scoring. In cellular experiments, cell adhesion and migration invasion ability were observed using phalloidin staining, cell scratch and transwell assays, respectively, and the expression of epithelial-mesenchymal transition-related markers was detected using quantitative reverse transcription polymerase chain reaction and western blotting. The results showed that ethanol-exposed mice lost more weight and had an increased number of esophageal nodules. Histological examination revealed that the lesion scores of the ethanol-exposed esophageal samples were significantly higher than those of the unexposed esophageal samples. Furthermore, ethanol-exposed esophageal cancer samples had more severe lesions with infiltration of tumor cells into the muscularis propria. In vitro cellular experiments showed that ethanol exposure induced cytoskeletal microfilament formation, promoted cell migration invasion elevated the expression of N-cadherin and Snail, and decreased the expression of E-cadherin. In conclusion, ethanol exposure exacerbates ESCC, promotes tumor cell infiltration into the muscularis propria, and could be an effective agent for establishing innovative models of invasive carcinoma.


Assuntos
4-Nitroquinolina-1-Óxido , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Etanol , Invasividade Neoplásica , Animais , 4-Nitroquinolina-1-Óxido/toxicidade , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Esofágicas/patologia , Etanol/toxicidade , Camundongos , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/induzido quimicamente , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Masculino , Humanos , Carcinogênese/induzido quimicamente , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Adesão Celular/efeitos dos fármacos
5.
Stem Cells ; 41(12): 1171-1184, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37659098

RESUMO

Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.


Assuntos
Insuficiência Hepática Crônica Agudizada , Células-Tronco Mesenquimais , Camundongos , Animais , Insuficiência Hepática Crônica Agudizada/metabolismo , Proteínas Tirosina Quinases/metabolismo , Macrófagos/metabolismo , Transdução de Sinais , Células-Tronco Mesenquimais/metabolismo , c-Mer Tirosina Quinase/genética , c-Mer Tirosina Quinase/metabolismo
6.
Cell Commun Signal ; 22(1): 460, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39342195

RESUMO

Medullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy that accounts for approximately 1-2% of all thyroid cancers (TCs). MTC include hereditary and sporadic cases, the former derived from a germline mutation of rearrangement during transfection (RET) proto-oncogene, whereas somatic RET mutations are frequently present in the latter. Surgery is the standard treatment for early stage MTC, and the 10-year survival rate of early MTC is over 80%. While for metastatic MTC, chemotherapy showing low response rate, and there was a lack of effective systemic therapies in the past. Due to the high risk (ca. 15-20%) of distant metastasis and limited systemic therapies, the 10-year survival rate of patients with advanced MTC was only 10-40% from the time of first metastasis. Over the past decade, targeted therapy for RET has developed rapidly, bringing hopes to patients with advanced and progressive MTC. Two multi-kinase inhibitors (MKIs) including Cabozantinib and Vandetanib have been shown to increase progression-free survival (PFS) for patients with metastatic MTC and have been approved as choices of first-line treatment. However, these MKIs have not prolonged overall survival (OS) and their utility is limited due to high rates of off-target toxicities. Recently, new generation TKIs, including Selpercatinib and Pralsetinib, have demonstrated highly selective efficacy against RET and more favorable side effect profiles, and gained approval as second-line treatment options. Despite the ongoing development of RET inhibitors, the management of advanced and progressive MTC remains challenging, drug resistance remains the main reason for treatment failure, and the mechanisms are still unclear. Besides, new promising therapeutic approaches, such as novel drug combinations and next generation RET inhibitors are under development. Herein, we overview the pathogenesis, molecular genetics and current management approaches of MTC, and focus on the recent advances of RET inhibitors, summarize the current situation and unmet needs of these RET inhibitors in MTC, and provide an overview of novel strategies for optimizing therapeutic effects.


Assuntos
Carcinoma Neuroendócrino , Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-ret/metabolismo , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais
7.
Neurochem Res ; 49(8): 2060-2074, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38814359

RESUMO

Since the clinical introduction of general anesthesia, its underlying mechanisms have not been fully elucidated. The ventral tegmental area (VTA) and parabrachial nucleus (PBN) play pivotal roles in the mechanisms underlying general anesthesia. However, whether dopaminergic (DA) projections from the VTA to the PBN play a role in mediating the effects of general anesthesia is unclear. We microinjected 6-hydroxydopamine into the PBN to damage tyrosine hydroxylase positive (TH+) neurons and found a prolonged recovery time from propofol anesthesia. We used calcium fiber photometry recording to explore the activity of TH + neurons in the PBN. Then, we used chemogenetic and optogenetic approaches either activate the VTADA-PBN pathway, shortening the propofol anesthesia emergence time, or inhibit this pathway, prolonging the emergence time. These data indicate the crucial involvement of TH + neurons in the PBN in regulating emergence from propofol anesthesia, while the activation of the VTADA-PBN pathway facilitates the emergence of propofol anesthesia.


Assuntos
Anestésicos Intravenosos , Neurônios Dopaminérgicos , Núcleos Parabraquiais , Propofol , Ratos Sprague-Dawley , Área Tegmentar Ventral , Propofol/farmacologia , Animais , Área Tegmentar Ventral/efeitos dos fármacos , Masculino , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Núcleos Parabraquiais/efeitos dos fármacos , Núcleos Parabraquiais/fisiologia , Anestésicos Intravenosos/farmacologia , Ratos , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Período de Recuperação da Anestesia , Oxidopamina/farmacologia
8.
Mol Pharm ; 21(9): 4312-4323, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39135316

RESUMO

Computational chemistry and machine learning are used in drug discovery to predict the target-specific and pharmacokinetic properties of molecules. Multiparameter optimization (MPO) functions are used to summarize multiple properties into a single score, aiding compound prioritization. However, over-reliance on subjective MPO functions risks reinforcing human bias. Mechanistic modeling approaches based on physiological relevance can be adapted to meet different potential key objectives of the project (e.g., minimizing dose, maximizing safety margins, and/or minimizing drug-drug interaction risk) while retaining the same underlying model structure. The current work incorporates recent approaches to predict in vivo pharmacokinetic (PK) properties and validates in vitro to in vivo correlation analysis to support mechanistic PK MPO. Examples of use and impact in small-molecule drug discovery projects are provided. Overall, the mechanistic MPO identifies 83% of the compounds considered as short-listed for clinical experiments in the top second percentile, and 100% in the top 10th percentile, resulting in an area under the receiver operating characteristic curve (AUCROC) > 0.95. In addition, the MPO score successfully recapitulates the chronological progression of the optimization process across different scaffolds. Finally, the MPO scores for compounds characterized in pharmacokinetics experiments are markedly higher compared with the rest of the compounds being synthesized, highlighting the potential of this tool to reduce the reliance on in vivo testing for compound screening.


Assuntos
Descoberta de Drogas , Humanos , Descoberta de Drogas/métodos , Aprendizado de Máquina , Bibliotecas de Moléculas Pequenas/farmacocinética , Farmacocinética , Área Sob a Curva , Animais , Curva ROC , Interações Medicamentosas
9.
Inorg Chem ; 63(31): 14308-14312, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39041605

RESUMO

Here, a case of bilayer heterojunction Pd-containing polyoxotungstate (POW), connecting a Te3Pd3 ring and an Anderson-like TeW6 cluster, has been synthesized. The Anderson-like cluster is the first example in POW. The coordination of Pd in the ring with the S atom on the sulfo group breaks the traditional coordination configuration of Pd and O in polyoxometalates (POMs), enriching the structural types of Pd-containing POMs. In addition, the hybrid bilayer heterojunction structure at the molecular level not only provides high thermal stability but also results in spatial arrangement anisotropy, leading to up to five times the anisotropic proton conductivity.

10.
Fish Shellfish Immunol ; 150: 109661, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38821227

RESUMO

IgNAR exhibits significant promise in the fields of cancer and anti-virus biotherapies. Notably, the variable regions of IgNAR (VNAR) possess comparable antigen binding affinity with much smaller molecular weight (∼12 kDa) compared to IgNAR. Antigen specific VNAR screening is a changeling work, which limits its application in medicine and therapy fields. Though phage display is a powerful tool for VNAR screening, it has a lot of drawbacks, such as small library coverage, low expression levels, unstable target protein, complicating and time-consuming procedures. Here we report VANR screening with next generation sequencing (NGS) could effectively overcome the limitations of phage display, and we successfully identified approximately 3000 BAFF-specific VNARs in Chiloscyllium plagiosum vaccinated with the BAFF antigen. The results of modelling and molecular dynamics simulation and ELISA assay demonstrated that one out of the top five abundant specific VNARs exhibited higher binding affinity to the BAFF antigen than those obtained through phage display screening. Our data indicates NGS would be an alternative way for VNAR screening with plenty of advantages.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Tubarões , Tubarões/imunologia , Tubarões/genética , Animais , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Antígenos/imunologia , Antígenos/genética , Doenças dos Peixes/imunologia
11.
Support Care Cancer ; 32(10): 649, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256232

RESUMO

PURPOSE: Despite the increasing research on cancer patient caregivers, there is still a lack of detailed understanding about the experiences of spouses caring for elderly colorectal cancer patients. This study aimed to fill this gap by examining the caregiving experiences of spouses during palliative chemotherapy for elderly Chinese colorectal cancer patients. METHODS: Using a qualitative descriptive design, we recruited spousal caregivers of elderly colorectal cancer patients undergoing palliative chemotherapy. Semistructured interviews were conducted, and thematic analysis was employed to analyse the data. RESULTS: Sixteen caregivers aged 60 to 82 years participated in the interviews. The analysis revealed three main themes: ambivalence, multiple role adaptation to conflicts, and the coexistence of hope and pressure. These themes shed light on the behaviors of older caregivers and the challenges they face, including physical and psychosocial issues associated with aging. CONCLUSION: This study highlights the significant stress and challenges experienced by older caregivers, characterized by intertwined emotions such as anxiety about their spouses' health deterioration, exhaustion from long-term care responsibilities, and anticipation of treatment outcomes.


Assuntos
Cuidadores , Neoplasias Colorretais , Cuidados Paliativos , Pesquisa Qualitativa , Humanos , Idoso , Cuidadores/psicologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/psicologia , Cuidados Paliativos/métodos , Cuidados Paliativos/psicologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Incerteza , Cônjuges/psicologia , Adaptação Psicológica , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Entrevistas como Assunto , China
12.
Support Care Cancer ; 32(8): 501, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985345

RESUMO

OBJECTIVE: This study aims to use structural equation modeling to explore the pathways and effect sizes of factors influencing the adherence of postoperative patients with digestive tract tumor to oral nutritional supplements, providing a theoretical basis for future nursing intervention measures. METHODS: A total of 300 postoperative patients with digestive tract tumor within 30 days after surgery were conveniently sampled. Surveys were conducted using a General Information Questionnaire, Morisky Medication Adherence Scale, Digestive System Tumor Patient Nutrition Knowledge-Attitude-Behavior Questionnaire, Multidimensional Social Perception Scale, Beliefs about Medical Questionnaire, and General Self-Efficacy Scale. Structural equation modeling was employed to analyze the factors and pathways affecting adherence with oral nutritional supplements. RESULTS: The adherence score of postoperative patients with digestive tract tumor to oral nutritional supplements was 1.61 ± 1.38. The structural equation model had a good fit (χ2/df = 2.685, GFI = 0.930, CFI = 0.913, AGFI = 0.887, IFI = 0.915, and RMSEA = 0.075). Nutrition knowledge, social support, medication beliefs, and self-efficacy were found to be factors influencing adherence with oral nutritional supplements in postoperative patients with digestive tract tumor, with total effects of 0.539, 0.264, 0.215, and 0.180, respectively. Nutrition knowledge indirectly affected adherence through self-efficacy and medication beliefs, while social support indirectly affected adherence through self-efficacy. CONCLUSION: Adherence with oral nutritional supplements in postoperative patients with digestive tract tumor is at a low level. Improving social support, enhancing patients nutrition knowledge, increasing self-efficacy, and strengthening medication beliefs are effective ways to improve patient adherence.


Assuntos
Suplementos Nutricionais , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação , Autoeficácia , Humanos , Estudos Transversais , Feminino , Masculino , Pessoa de Meia-Idade , Adesão à Medicação/estatística & dados numéricos , Inquéritos e Questionários , Idoso , Adulto , Neoplasias do Sistema Digestório/cirurgia , Neoplasias do Sistema Digestório/psicologia , Apoio Social , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/psicologia , Período Pós-Operatório
13.
Environ Res ; 263(Pt 1): 120019, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39284489

RESUMO

This study investigates the role of Government Social Media (GSM) in enhancing public engagement with Low-Carbon Practices (LCP) in Japan. Motivated by the need to foster sustainable development and mitigate climate change impacts, this research utilizes negative binomial regression model analyzing 1022 posts from nine Japanese government social media accounts. Our findings reveal that increased media richness negatively correlates with engagement, suggesting that content depth over visual appeal is more effective for LCP-related communication. Surprisingly, the dialogic loop reduces engagement, indicating complex public reactions to governmental initiatives. Content themes related to governmental actions and LCP information significantly enhance engagement, while emotional valence shows minimal impact. The study introduces 'social media capital' as a moderating factor, which mitigates the negative effects of dialogic loops and media richness on engagement, and influences the impact of content themes. These insights provide a foundation for future research and guide the development of effective public engagement strategies in environmental policy. The study highlights the need for nuanced GSM strategies that prioritize information quality and relevance to increase public participation in low-carbon initiatives.

14.
Mol Divers ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009908

RESUMO

Accumulated research strongly indicates that Janus kinase 3 (JAK3) is intricately involved in the initiation and advancement of a diverse range of human diseases, underscoring JAK3 as a promising target for therapeutic intervention. However, JAK3 shows significant homology with other JAK family isoforms, posing substantial challenges in the development of JAK3 inhibitors. To address these limitations, one strategy is to design selective covalent JAK3 inhibitors. Therefore, this study introduces a virtual screening approach that combines common feature pharmacophore modeling, covalent docking, and consensus scoring to identify novel inhibitors for JAK3. First, common feature pharmacophore models were constructed based on a selection of representative covalent JAK3 inhibitors. The optimal qualitative pharmacophore model proved highly effective in distinguishing active and inactive compounds. Second, 14 crystal structures of the JAK3-covalent inhibitor complex were chosen for the covalent docking studies. Following validation of the screening performance, 5TTU was identified as the most suitable candidate for screening potential JAK3 inhibitors due to its higher predictive accuracy. Finally, a virtual screening protocol based on consensus scoring was conducted, integrating pharmacophore mapping and covalent docking. This approach resulted in the discovery of multiple compounds with notable potential as effective JAK3 inhibitors. We hope that the developed virtual screening strategy will provide valuable guidance in the discovery of novel covalent JAK3 inhibitors.

15.
Nephrology (Carlton) ; 29(9): 588-599, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38689467

RESUMO

AIM: Kidney transplant recipients are at high risk of fracture due to many factors such as nutritional status, hyperparathyroidism, acidosis and steroid administration. The current meta-analysis aimed to comprehensively analyse the incidence and risk factors of fracture in kidney transplant recipients. METHODS: A systematic search on Embase, Web of Science, PubMed and Cochrane Library until November 2023 was performed. RStudio software was used to analyse data. RESULTS: Twenty-eight eligible studies containing 310 530 kidney transplant recipients were included in the analysis. The pooled incidence of fracture was 10% (95% confidence interval [CI]: 7%-13%) generally. When divided by regions, it was further observed that the pooled incidence of fracture was 13% (95% CI: 9%-17%) in Europe, 11% (95% CI: 6%-16%) in North America, 7% (95% CI: 3%-11%) in Asia. Regarding the risk factors, pooled analysis revealed that age of recipient (hazard ratio [HR] = 1.50, 95% CI: 1.17-1.91), female sex (HR = 1.45, 95% CI: 1.36-1.53), pretransplantation diabetes (HR = 1.76, 95% CI: 1.58-1.97), pretransplantation fracture history (HR = 2.28, 95% CI: 1.86-2.78), dialysis duration (HR = 1.09, 95% CI: 1.01-1.17) and deceased donor (HR = 1.21, 95% CI: 1.05-1.39) related to higher risk of fracture. The general quality of included studies was acceptable, and no publication bias existed except for the analysis between age of recipient and fracture incidence; further trim and fill method indicated age of recipient showed a correlation trend with the fracture incidence without the statistical significance. CONCLUSION: The pooled incidence of fracture reaches 10% in kidney transplant recipients, which relates to age of recipient, female sex, pretransplantation diabetes or fracture history, dialysis duration and decease donor.


Assuntos
Fraturas Ósseas , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Fatores de Risco , Incidência , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Transplantados/estatística & dados numéricos , Feminino
16.
Mikrochim Acta ; 191(4): 225, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557876

RESUMO

An intelligent fluorescent nanoprobe (lignite-CDs-Eu) was constructed by an effective and facile method based on lignite-derived carbon dots (CDs) and lanthanide europium ions (Eu3+), which exhibited high sensitivity, low detection limit (13.35 nM) and visual color variation (from blue to red) under ultraviolet light towards tetracycline (TC) detection. Significantly, portable and economical sensors were developed using lignite-CDs-Eu immobilized fiber material of filter paper and wearable glove with the aid of color extracting and image processing application (APP) in the smartphone. Facile, fast and real-time visual detection of TC in food samples was realized. Moreover, logic gate circuit was also designed to achieve intelligent and semi-quantitative inspection of TC. To some extent, this study extended the cross-application of intelligent computer software in food analytical science, and provided a certain reference for the development of small portable detection sensors which were suitable for convenience and non-professional use in daily life.


Assuntos
Elementos da Série dos Lantanídeos , Tetraciclina , Antibacterianos , Európio , Carvão Mineral
17.
Mikrochim Acta ; 191(9): 531, 2024 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134877

RESUMO

Tetracycline (TC) has been widely used in clinical medicine and animal growth promotion due to its broad-spectrum antibacterial properties and affordable prices. Unfortunately, the high toxicity and difficult degradation rate of TC molecules make them easy to accumulate in the environment, which breaks the ecological balance and seriously threatens human health. Rapid and accurate detection of TC residue levels is important for ensuring water quality and food safety. Recently, fluorescence detection technology of TC residues has developed rapidly. Lanthanide nanomaterials, based on the high luminescence properties of lanthanide ions and the high matching with TC energy levels, are favored in the real-time trace detection of TC due to their advantages of high sensitivity, rapidity, and high selectivity. Therefore, they are considered potential substitutes for traditional detection methods. This review summarizes the synthesis strategy, TC response mechanism, removal mechanism, and applications in intelligent sensing. Finally, the development of lanthanide nanomaterials for TC fluorescence detection and removal is reasonably summarized and prospected. This review provides a reference for the establishment of a method for the accurate determination of TC content in complex food matrices.


Assuntos
Corantes Fluorescentes , Elementos da Série dos Lantanídeos , Tetraciclina , Elementos da Série dos Lantanídeos/química , Tetraciclina/análise , Tetraciclina/química , Corantes Fluorescentes/química , Nanoestruturas/química , Antibacterianos/análise , Antibacterianos/química , Humanos , Espectrometria de Fluorescência/métodos , Contaminação de Alimentos/análise
18.
Genomics ; 115(6): 110737, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37926353

RESUMO

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.


Assuntos
Insuficiência Hepática Crônica Agudizada , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Insuficiência Hepática Crônica Agudizada/genética , Insuficiência Hepática Crônica Agudizada/terapia , Insuficiência Hepática Crônica Agudizada/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células-Tronco Mesenquimais/metabolismo
19.
BMC Nurs ; 23(1): 380, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840132

RESUMO

BACKGROUND: Oral nutritional supplements are one of the preferred methods of nutritional support for postoperative patients. This study aims to investigate the current status of oral nutritional supplements compliance in postoperative patients with digestive tract tumors and its influencing factors. METHODS: Convenience sampling was employed to select 242 patients who underwent surgery for digestive tract tumors at a tertiary hospital in Shanghai from October 2022 to July 2023 as the study subjects. Data following a normal distribution were analyzed using independent sample t-tests, ANOVA single-factor analysis, Pearson correlation analysis, and multiple linear regression analysis to determine the factors influencing compliance with oral nutritional supplements. RESULTS: A total of 252 questionnaires were distributed, with 10 invalid questionnaires excluded, resulting in an effective questionnaire rate of 96.03%. The compliance score for oral nutritional supplements in postoperative patients with digestive tract tumors was (2.40 ± 1.45), General Self-efficacy Scale (GSES) score was (24.72 ± 4.86), Multidimensional Scale of Perceived Social Support Scale (MSPSS) score was (58.67 ± 11.09), and Belief about Medicines Questionnaire Scale (BMQ) score was (0.17 ± 2.78). Multiple linear regression analysis revealed that age, adverse reactions, educational level, self-efficacy, medication beliefs, and social support were factors influencing compliance with oral nutritional supplements in postoperative patients with digestive tract tumors (P < 0.05). CONCLUSION: Our study revealed that the compliance to oral nutritional supplements among postoperative patients with digestive tract tumors was at a moderate level and was closely associated with age, educational level, adverse reactions to oral nutritional supplements, medication beliefs, social support, and self-efficacy. Nursing staff should conduct nursing assessments based on the specific circumstances of patients and their families, provide personalized health education management plans based on the patients' educational level, enhance patients' nutrition knowledge, improve patient self-efficacy, and enhance social support for patients, while further improving patient nutrition management.

20.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(1): 54-61, 2024 Jan 15.
Artigo em Zh | MEDLINE | ID: mdl-38269460

RESUMO

OBJECTIVES: To explore the relationship of triglyceride-glucose index (TyG), triglyceride-glucose-body mass index (TyG-BMI), and triglyceride-glucose-waist circumference index (TyG-WC) with blood pressure abnormalities in adolescents, providing theoretical basis for the prevention and control of hypertension in adolescents. METHODS: A stratified cluster sampling method was used to select 1 572 adolescents aged 12 to 18 years in Yinchuan City for questionnaire surveys, physical measurements, and laboratory tests. Logistic regression analysis and restricted cubic spline analysis were employed to examine the relationship of TyG, TyG-BMI, and TyG-WC with blood pressure abnormalities in adolescents. RESULTS: Multivariable logistic regression analysis revealed that after adjusting for confounding factors, the groups with the highest quartile of TyG, TyG-BMI, and TyG-WC had 1.48 times (95%CI: 1.07-2.04), 3.71 times (95%CI: 2.67-5.15), and 4.07 times (95%CI: 2.89-5.73) higher risks of blood pressure abnormalities compared to the groups with the lowest quartile, respectively. Moreover, as the levels of TyG, TyG-BMI, and TyG-WC increased, the risk of blood pressure abnormalities gradually increased (P<0.05). A non-linear dose-response relationship was observed between TyG-BMI and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.002). Linear dose-response relationships were found between TyG and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearit =0.232), and between TyG-WC and the risk of blood pressure abnormalities (P overall trend<0.001, P non-linearity=0.224). CONCLUSIONS: Higher levels of TyG and its derivatives are associated with an increased risk of blood pressure abnormalities in adolescents, with linear or non-linear dose-response relationships.


Assuntos
Hipertensão , Adolescente , Humanos , Pressão Sanguínea , Índice de Massa Corporal , Hipertensão/epidemiologia , Hipertensão/etiologia , Glucose , Triglicerídeos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA