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1.
J Multidiscip Healthc ; 17: 2313-2320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774624

RESUMO

Purpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD). Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test. Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23±6.17 VS 7.89±2.38). The difference between the two groups had statistical significance (P < 0.05). Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.

2.
Poult Sci ; 103(6): 103745, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38670058

RESUMO

Fowl adenovirus serotype 11 (FAdV-11) is one of the main causative agents of inclusion body hepatitis (IBH) in broilers. Outbreaks of FAdV-11-related IBH have been increasingly reported in China and many other geographical areas worldwide. However, the critical virulence factors of FAdV-11 remain uncertain due to the lack of technical platforms for efficient manipulation of FAdV-11 genome. Here, we reported the establishment of a FAdV-11 reverse genetic system based on a novel FAdV-11 Chinese isolate FJSW/2021 using the exonuclease combined with RecET (ExoCET), Redαß recombineering and ccdB counter-selection techniques for the first time. A recombinant FAdV-11 was rescued efficiently by using the established reverse genetic platform through swapping the ORF11 gene of the FAdV-11 FJSW/2021 with the ZsGreen fluorescent protein expression cassette. This study provides an effective technical platform for identifying virulence factors of FAdV-11 and developing recombinant FAdV-11-vectored vaccine candidates.

3.
J Med Chem ; 67(8): 6425-6455, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38613499

RESUMO

The RAS-RAF-MEK-ERK signaling cascade is abnormally activated in various tumors, playing a crucial role in mediating tumor progression. As the key component at the terminal stage of this cascade, ERK1/2 emerges as a potential antitumor target and offers a promising therapeutic strategy for tumors harboring BRAF or RAS mutations. Here, we identified 36c with a (thiophen-3-yl)aminopyrimidine scaffold as a potent ERK1/2 inhibitor through structure-guided optimization for hit 18. In preclinical studies, 36c showed powerful ERK1/2 inhibitory activities (ERK1/2 IC50 = 0.11/0.08 nM) and potent antitumor efficacy both in vitro and in vivo against triple-negative breast cancer and colorectal cancer models harboring BRAF and RAS mutations. 36c could directly inhibit ERK1/2, significantly block the phosphorylation expression of their downstream substrates p90RSK and c-Myc, and induce cell apoptosis and incomplete autophagy-related cell death. Taken together, this work provides a promising ERK1/2 lead compound for multiple tumor-treatment drug discovery.


Assuntos
Antineoplásicos , Inibidores de Proteínas Quinases , Pirimidinas , Humanos , Pirimidinas/farmacologia , Pirimidinas/síntese química , Pirimidinas/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Relação Estrutura-Atividade , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Tiofenos/farmacologia , Tiofenos/síntese química , Tiofenos/química , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Linhagem Celular Tumoral , Descoberta de Drogas , Apoptose/efeitos dos fármacos , Feminino , Camundongos Nus , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C
4.
BMC Public Health ; 24(1): 698, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443876

RESUMO

BACKGROUND: Opioid crisis has become a global concern, but whether physical activity (PA) can effectively reduce prescription opioid use remains unclear. The study aimed to examine the relationship of different domains of PA (e.g., occupation-related PA [OPA], transportation-related PA [TPA], leisure-time PA [LTPA]) with prescription opioid use and duration of prescription opioid use. METHODS: This cross-sectional study was conducted on 27,943 participants aged ≥ 18 years from National Health and Nutrition Examination Survey (NHANES, 2007- March 2020). We examined the relationship of different domains of PA with prescription opioid use and duration of prescription opioid use using multivariable logistic regression. Stratified analysis and a series of sensitivity analysis were used to elevate robustness. All analyses were conducted using appropriate sampling weights. RESULTS: Of the 27,943 participants, the mean age was 45.10 years, with 14,018 [weighted, 50.0%] females and 11,045 [weighted, 66.0%] non-Hispanic White. After multivariable adjustment, inverse associations between PA and prescription opioid use were observed for sufficient (≥ 150 min/week) total PA (OR,0.68 95%CI [0.56-0.81]), TPA (OR,0.73 95%CI [0.58-0.92]), and LTPA (OR,0.60 95%CI [0.48-0.75]) compared with insufficient PA(< 150 min/week), but not for sufficient OPA (OR,0.93 95%CI [0.79-1.10]). In addition, the associations were dose-responsive, participants had 22-40%, 27-36%, and 26-47% lower odds of using prescription opioids depending on the duration of total PA, TPA, and LTPA, respectively. Nevertheless, the impact of PA on prescription opioid use varied by duration of opioid use. Sufficient total PA was associated with elevated odds of short-term use of prescription opioids (< 90 days). Comparatively, sufficient total PA, TPA, and LTPA had different beneficial effects on reducing long-term use of prescription opioids (≥ 90 days) depending on the strength of opioids. CONCLUSIONS: This study demonstrated sufficient total PA, TPA, and LTPA were inversely associated with prescription opioid use and varied depending on the duration and strength of prescription opioid use. These findings highlight PA can provide policy guidance to address opioid crisis.


Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Inquéritos Nutricionais , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Exercício Físico , Prescrições
5.
Anticancer Drugs ; 35(6): 525-534, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38502854

RESUMO

Salidroside is a natural product of phenols with a wide range of pharmacological functions, but whether it plays a role in regulating autophagy is unclear. We systematically investigated the regulatory effect and molecular mechanism of salidroside on autophagy through network pharmacology, which provided a theoretical basis for subsequent experimental research. First, the target genes of salidroside were obtained using the Chinese Medicine System Pharmacology Database and Analysis Platform, and the target genes were converted into standardized gene names using the Uniprot website. At the same time, autophagy-related genes were collected from GeneCards, and preliminary handling of data to obtain intersecting genes. Then, the String website was used to construct a protein-protein interaction network, and to perform the Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis. To observe the specific molecular mechanism by which salidroside regulates autophagy, we constructed a drug component-target genes-autophagy network. Finally, we performed molecular docking to verify the possible binding conformation between salidroside and the candidate target. By searching the database and analyzing the data, we found that 113 target genes in salidroside interact with autophagy. Salidroside regulate autophagy in relation to a number of important oncogenes and signaling pathways. Molecular docking confirmed that salidroside has high affinity with mTOR, SIRT1, and AKT1. Through network pharmacology combined with molecular docking-validated research methods, we revealed the underlying mechanism of salidroside regulation of autophagy. This study not only provides new systematic insights into the underlying mechanism of salidroside in autophagy, but also provides new ideas for network approaches for autophagy-related research.


Assuntos
Autofagia , Glucosídeos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fenóis , Autofagia/efeitos dos fármacos , Fenóis/farmacologia , Fenóis/química , Glucosídeos/farmacologia , Humanos , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
6.
Poult Sci ; 103(5): 103642, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537408

RESUMO

Fowl adenovirus serotype 11 (FAdV-11) is one of the primary causative agents of inclusion body hepatitis (IBH), which causes substantial economic losses in the world poultry industry. In this study, we characterized the genome of the fowl adenovirus serotype 11 (FAdV-11) isolate FJSW/2021. The full genome of FJSW/2021 was 44, 154 base pairs (bp) in length and had a similar organization to that of previously reported FAdV-11 isolates. Notably, compared with those of other reported FAdV-11 strains, the preterminal protein (pTP) of FAdV-11 FJSW/2021 has six amino acid (aa) insertions (S-L-R-I-I-C) between 470 and 475 and one aa mutation of L476F; moreover, the tandem repeat (TR) regions of TR1 and TR2 were 33 bp (1 repeat) and 1,080 bp (8 repeats) shorter than those of the Canadian nonpathogenic isolate ON NP2, respectively. The pathogenicity of FJSW/2021 was studied in 10-day-old specific pathogen-free chicken embryos following allantoic cavity inoculation and in 1-day-old, 1-wk-old and 2-wk-old SPF chickens following intramuscular inoculation with 107 TCID50 of the virus. The results showed that FJSW/2021 can induce typical severe IBH in chicks less than 2 wk old. These findings highlighted the genetic differences between the pathogenic and non-pathogenic FAdV-11 isolates. The data will provide guidance for identifying the virulence factors of FAdV-11 strains. The animal challenge model developed in our study will allow precise evaluation of the efficacy of potential FAdV-11 vaccine candidates.


Assuntos
Aviadenovirus , Galinhas , Genoma Viral , Doenças das Aves Domésticas , Sorogrupo , Animais , Doenças das Aves Domésticas/virologia , China , Aviadenovirus/genética , Aviadenovirus/patogenicidade , Virulência , Organismos Livres de Patógenos Específicos , Hepatite Viral Animal/virologia , Embrião de Galinha , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia
7.
J Med Chem ; 67(4): 2777-2801, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38323982

RESUMO

Activation of the alternative pathways and abnormal signaling transduction are frequently observed in third-generation EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors)-resistant patients. Wherein, hyperphosphorylation of ACK1 contributes to EGFR-TKIs acquired resistance. Dual inhibition of EGFRL858R/T790M and ACK1 might improve therapeutic efficacy and overcome resistance in lung cancers treatment. Here, we identified a EGFRL858R/T790M/ACK1 dual-targeting compound 21a with aminoquinazoline scaffold, which showed excellent inhibitory activities against EGFRL858R/T790M (IC50 = 23 nM) and ACK1 (IC50 = 263 nM). The cocrystal and docking analysis showed that 21a occupied the ATP binding pockets of EGFRL858R/T790M and ACK1. Moreover, 21a showed potent antiproliferative activities against the H1975 cells, MCF-7 cells and osimertinib-resistant cells AZDR. Further, 21a showed significant antitumor effects and good safety in ADZR xenograft-bearing mice. Taken together, 21a was a potent dual inhibitor of EGFRL858R/T790M/ACK1, which is deserved as a potential lead for overcoming acquired resistance to osimertinib during the EGFR-targeted therapy.


Assuntos
Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Pirimidinas , Humanos , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Receptores ErbB/metabolismo , Resistencia a Medicamentos Antineoplásicos , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/química , Linhagem Celular Tumoral
8.
Diagn Pathol ; 19(1): 23, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291475

RESUMO

OBJECTIVE: This study aimed to investigate the clinicopathological features and prognostic indicators of alveolar soft part sarcoma (ASPS). METHODS: The characteristics of 26 ASPS patients diagnosed at our hospital between January 2011 and January 2019 were retrospectively analysed. RESULTS: The data for 12 male and 14 female patients, with a median age of 27.5 years, were assessed. The clinical symptoms mainly included painless enlarged masses in deep soft tissues. ASPS had a characteristic pathological morphology. Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients. Among the 26 patients who completed follow-up, 14 had metastasis, 1 had local recurrence, and 7 died. Kaplan-Meier survival analysis revealed that prognosis was significantly correlated with sex, tumour size and metastasis (P < 0.05). Multivariate Cox regression analysis revealed that sex and metastasis were independent prognostic risk factors for patients with ASPS (P < 0.05). CONCLUSION: ASPS is a rare soft tissue sarcoma of unknown origin that occurs in young people, has a slow but metastatic course, and is associated with a poor 5-year survival rate among patients with metastasis. ASPS has character TFE3 protein and gene expression, and the diagnosis is relatively specific. The diagnosis requires comprehensive analysis of clinical history, histological morphology, and immunohistochemistry.


Assuntos
Sarcoma Alveolar de Partes Moles , Humanos , Masculino , Feminino , Adolescente , Adulto , Estudos Retrospectivos , Sarcoma Alveolar de Partes Moles/diagnóstico , Sarcoma Alveolar de Partes Moles/genética , Sarcoma Alveolar de Partes Moles/patologia , Prognóstico , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Risco
9.
Comput Biol Med ; 170: 107989, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286105

RESUMO

Accurate segmentation of the pancreas from abdominal computed tomography (CT) images is challenging but essential for the diagnosis and treatment of pancreatic disorders such as tumours and diabetes. In this study, a dataset with 229 sets of high-resolution CT images was generated and annotated. We proposed a novel 3D segmentation model named nnTransfer (nonisomorphic transfer learning) net, which employs generative model structure for self-supervision to facilitate the network's learning of image attributes from unlabelled data. The effectiveness for pancreas segmentation of nnTransfer was assessed using the Hausdorff distance (HD) and Dice similarity coefficient (DSC) on the dataset. Additionally, a histogram analysis with local thresholding was used to achieve automated whole-volume measurement of pancreatic fat (fat volume fraction, FVF). The proposed technique performed admirably on the dataset, with DSC: 0.937 ± 0.019 and HD: 2.655 ± 1.479. The mean pancreas volume and FVF of the pancreas were 91.95 ± 23.90 cm3 and 12.67 % ± 9.84 %, respectively. The nnTransfer functioned flawlessly and autonomously, facilitating the use of the FVF to evaluate pancreatic disease, particularly in patients with diabetes.


Assuntos
Aprendizado Profundo , Diabetes Mellitus , Humanos , Processamento de Imagem Assistida por Computador/métodos , Pâncreas/diagnóstico por imagem , Tomografia Computadorizada por Raios X
10.
World J Clin Cases ; 11(34): 8164-8169, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38130781

RESUMO

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disease of Langerhans cells with unknown pathogenesis. An increasing number of clinicians recognize that LCH has a wide clinical spectrum and a highly varied course. Adults rarely develop LCH. Here, we report a case of adult localized LCH. CASE SUMMARY: A 32-year-old woman presented with plaques and ulcers on the vulva and crissum, accompanied by pain that persisted for more than one year. Physical examination revealed a red-infiltrating plaque with ulcerations and exudates in the vulva and crissum. Pathological examination revealed a diffuse infiltration of lymphocytes, eosinophilic granulocytes, and histiocytoid cells in the superficial dermis. Proliferative histiocytoid cells showed mild atypia, partly with kidney-shaped nuclei. Immunohistochemical examination showed that the histiocytoid cells were positive for S100 protein and CD1 and weakly positive for CD68 (20% +), with a Ki-67 index of 30%. Laboratory tests did not reveal any other systemic damage. The patient was diagnosed with adult localized LCH and was prescribed oral prednisone (20 mg) once daily. The skin lesions gradually improved and are still being followed-up. CONCLUSION: Adult localized LCH is rare and must be differentiated from other common conditions.

11.
Headache ; 63(10): 1341-1350, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37938023

RESUMO

OBJECTIVE: The study aimed to examine the relationship between secondhand smoke (SHS) exposure and severe headaches or migraine in never-smoking adults verified by serum cotinine. BACKGROUND: Current evidence about the association between self-reported SHS exposure and headaches or migraine is limited and contradictory. An important issue lies in the lack of actual SHS exposure assessment through biomarkers. METHODS: We conducted a cross-sectional study on 4560 never-smoking adults from the National Health and Nutrition Examination Survey (NHANES), 1999-2004. The SHS exposure was evaluated by measuring serum cotinine concentrations. The information regarding severe headaches or migraine was based on self-reporting. RESULTS: The overall prevalence rate of severe headaches or migraine was 20% (919/4560). After adjusting for relevant covariates, we found that heavy SHS exposure (serum cotinine at 1 to 10 ng/mL) was positively associated with severe headaches or migraine (OR: 2.02, 95% CI [1.19, 3.43]); however, no significant association was found between low SHS exposure (serum cotinine at 0.05 to 0.99 ng/mL) and severe headaches or migraine (OR: 1.15, 95% CI [0.91, 1.47]). Restricted cubic spline analysis showed that the natural logarithm of serum cotinine had a linear relationship with severe headaches or migraine (p = 0.335 for nonlinearity). Stratified analysis indicated that individuals with a BMI of <25 (p < 0.001 for interaction) and sedentary activity (p = 0.016 for interaction) modified the relationship between SHS exposure and severe headaches and migraine. Even after altering the definition of SHS exposure, excluding drugs that might affect the metabolism of serum cotinine, and multiple imputation, our sensitivity analysis results remained stable. CONCLUSIONS: The study demonstrated that heavy SHS exposure (serum cotinine at 1 to 10 ng/mL) had a significant positive association with severe headaches or migraine in never-smoking adults. Prospective studies are necessary to verify this relationship in the future.


Assuntos
Transtornos de Enxaqueca , Poluição por Fumaça de Tabaco , Humanos , Adulto , Inquéritos Nutricionais , Poluição por Fumaça de Tabaco/efeitos adversos , Cotinina/análise , Estudos Transversais , Estudos Prospectivos , Transtornos de Enxaqueca/epidemiologia , Cefaleia/epidemiologia , Cefaleia/etiologia , Fumar
12.
Nurs Open ; 10(12): 7467-7486, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37789573

RESUMO

AIM: To synthesize self-administrated needs assessment tools of informal caregivers for patients with chronic non-communicable diseases (CNCDs), evaluate the quality of psychometric properties and identify main needs assessment themes. DESIGN: Systematic review. METHODS: Eight electronic databases both in English and Chinese were searched for. The psychometric properties of tools were evaluated according to the quality criteria for good psychometric properties developed by Terwee et al. Both the content analysis and thematic extraction methods were used. Needs assessment themes were categorized based on the 7-level Maslow's Hierarchy of Needs Theory. RESULTS: A total of 17 tools were synthesized. Thirteen of them targeted informal caregivers of patients with cancer. The psychometric properties evaluated for most of these tools were content validity, internal consistency and construct validity. A total of 27 needs themes were identified and matched to six levels based on the 7-level Maslow's Hierarchy of Needs theory, besides the aesthetic needs level. NO PATIENT OR PUBLIC CONTRIBUTION: No primary data are being collected.


Assuntos
Cuidadores , Doenças não Transmissíveis , Humanos , Autoavaliação (Psicologia) , Inquéritos e Questionários , Avaliação das Necessidades
13.
Nat Commun ; 14(1): 6190, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794006

RESUMO

As the unique cell type in articular cartilage, chondrocyte senescence is a crucial cellular event contributing to osteoarthritis development. Here we show that clathrin-mediated endocytosis and activation of Notch signaling promotes chondrocyte senescence and osteoarthritis development, which is negatively regulated by myosin light chain 3. Myosin light chain 3 (MYL3) protein levels decline sharply in senescent chondrocytes of cartilages from model mice and osteoarthritis (OA) patients. Conditional deletion of Myl3 in chondrocytes significantly promoted, whereas intra-articular injection of adeno-associated virus overexpressing MYL3 delayed, OA progression in male mice. MYL3 deficiency led to enhanced clathrin-mediated endocytosis by promoting the interaction between myosin VI and clathrin, further inducing the internalization of Notch and resulting in activation of Notch signaling in chondrocytes. Pharmacologic blockade of clathrin-mediated endocytosis-Notch signaling prevented MYL3 loss-induced chondrocyte senescence and alleviated OA progression in male mice. Our results establish a previously unknown mechanism essential for cellular senescence and provide a potential therapeutic direction for OA.


Assuntos
Cartilagem Articular , Osteoartrite , Humanos , Masculino , Camundongos , Animais , Condrócitos/metabolismo , Cadeias Leves de Miosina/metabolismo , Senescência Celular/fisiologia , Osteoartrite/genética , Osteoartrite/metabolismo , Cartilagem Articular/metabolismo , Endocitose
14.
Sci Rep ; 13(1): 14114, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644107

RESUMO

Salidroside is a natural product of phenols, which has a wide scape of pharmacological effects, but its pharmacological effects and molecular mechanism on endometrial cancer are not clear. To systematically explore the pharmacological effects and molecular mechanisms of salidroside on endometrial cancer through the method of network pharmacology. The possible target genes of salidroside were obtained through different pharmacological databases and analysis platforms, and then the relevant target genes of endometrial cancer were obtained through the GeneCards website, and the target genes were uniformly converted into standardized gene names with Uniprot. The collected data were then processed to obtain common target genes and further analyzed through the String website to construct a protein-protein interaction (PPI) network, followed by gene ontology (GO) functional annotation and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analysis. We further interpreted the molecular mechanism of salidroside for the treatment of endometrial cancer by constructing a "drug component-target gene-disease" network. Finally, we performed molecular docking to validate the binding conformation between salidroside and the candidate target genes. There were 175 target genes of salidroside after normalization, among which 113 target genes interacted with endometrial cancer. GO analysis indicated that the anti-endometrial cancer effect of salidroside may be strongly related to biological processes such as apoptosis and response to drug. KEGG analysis indicated that its mechanism may be related to pathway in cancer and PI3K-AKT signaling pathway. Molecular docking showed that salidroside had high affinity with five key genes. Based on the novel network pharmacology and molecular docking validation research methods, we have revealed for the first time the potential mechanism of salidroside in the therapy of endometrial cancer.


Assuntos
Neoplasias do Endométrio , Farmacologia em Rede , Feminino , Humanos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Fenóis/farmacologia , Fenóis/uso terapêutico
15.
J Oral Biosci ; 65(4): 347-355, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37625505

RESUMO

OBJECTIVES: This study aimed to explore the role and specific mechanism of the cholesterol-lowering drug simvastatin in inhibiting oral squamous cell carcinoma (OSCC). METHODS: The proliferation, apoptosis, and migration levels of OSCC cells were detected by CCK8, quantitative real-time polymerase chain reaction, Western blot, colony formation, TdT-mediated dUTP Nick-End Labeling assay, and wound healing assay. The inhibitory effect of simvastatin in vivo was detected by a mouse xenograft tumor model. Immunohistochemistry and immunofluorescence staining were used to assess the KLF2 and ß-catenin expressions in cells and tissues. RESULTS: KLF2 expression in OSCC cells and tissues was downregulated. The addition of KLF2 inducer, GGTI298, inhibited the proliferation and migration of OSCC cells. Simvastatin played a role in inhibiting the proliferation and promoting the apoptosis of OSCC cells. Moreover, it inhibited ß-catenin expression and promoted KLF2 expression in OSCC cells. KLF2 siRNA reversed the effect of simvastatin on the proliferation and apoptosis of OSCC cells. CONCLUSIONS: KLF2, as a tumor suppressor gene, may be an important marker for diagnosing and treating OSCC. Simvastatin inhibits the progression of OSCC by regulating the KLF2 signal.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , beta Catenina/genética , beta Catenina/metabolismo , beta Catenina/farmacologia , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Apoptose/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/farmacologia
16.
ACS Biomater Sci Eng ; 9(8): 4761-4769, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37424070

RESUMO

Since the physical properties are similar to native extracellular matrices, double network (DN) hydrogels have been studied extensively in the tissue engineering. However, the double chemical crosslinked DN hydrogel is limited by poor fatigue resistance. π-π stacking is a non-covalent bonding interaction, which is essential to maintain and self-assemble the three-dimensional structure of biological proteins and nucleic acids. In this study, a robust polyethylene glycol diacrylate (PEGDA)/FFK hybrid DN hydrogel was prepared by Michael addition and π-π stacking. The hybrid DN hydrogels with π-π stacking interactions have excellent mechanical strength and fatigue resistance. The DN FFK/PEGDA hydrogels reveal great biocompatibility and hemocompatibility. The DN hydrogels containing π-π stacking have the potential to fabricate robust hybrid DN hydrogels in drug release and tissue engineering.


Assuntos
Materiais Biocompatíveis , Hidrogéis , Hidrogéis/química , Peptídeos , Engenharia Tecidual , Matriz Extracelular
17.
Cancer Imaging ; 23(1): 71, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488597

RESUMO

BACKGROUND: To build and validate a radiomics nomogram based on preoperative CT scans and clinical data for detecting synchronous ovarian metastasis (SOM) in female gastric cancer (GC) cases. METHODS: Pathologically confirmed GC cases in 2 cohorts were retrospectively enrolled. All cases had presurgical abdominal contrast-enhanced CT and pelvis contrast-enhanced MRI and pathological examinations for any suspicious ovarian lesions detected by MRI. Cohort 1 cases (n = 101) were included as the training set. Radiomics features were obtained to develop a radscore. A nomogram combining the radscore and clinical factors was built to detect SOM. The bootstrap method was carried out in cohort 1 as internal validation. External validation was carried out in cohort 2 (n = 46). Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) and the confusion matrix were utilized to assess the performances of the radscore, nomogram and subjective evaluation model. RESULTS: The nomogram, which combined age and the radscore, displayed a higher AUC than the radscore and subjective evaluation (0.910 vs 0.827 vs 0.773) in the training cohort. In the external validation cohort, the nomogram also had a higher AUC than the radscore and subjective evaluation (0.850 vs 0.790 vs 0.675). DCA and the confusion matrix confirmed the nomogram was superior to the radscore in both cohorts. CONCLUSIONS: This pilot study showed that a nomogram model combining the radscore and clinical characteristics is useful in detecting SOM in female GC cases. It may be applied to improve clinical treatment and is superior to subjective evaluation or the radscore alone.


Assuntos
Cistos Ovarianos , Neoplasias Ovarianas , Neoplasias Gástricas , Humanos , Feminino , Nomogramas , Projetos Piloto , Estudos Retrospectivos
18.
Gene ; 874: 147485, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37187246

RESUMO

Lilium pumilum has a strong salt tolerance. However, the molecular mechanism underlying its salt tolerance remains unexplored. Here, LpSOS1 was cloned from L. pumilum and found to be significantly enriched at high NaCl concentrations (100 mM). In tobacco epidermal cells, localization analysis showed that the LpSOS1 protein was primarily located in the plasma membrane. Overexpression of LpSOS1 resulted in up-regulation of salt stress tolerance in Arabidopsis, as indicated by reduced malondialdehyde levels and Na+/K+ ratio, and increased activity of antioxidant reductases (including superoxide dismutase, peroxidase, and catalase). Treatment with NaCl resulted in improved growth, as evidenced by increased biomass, root length, and lateral root growth, in both sos1 mutant (atsos1) and wild-type (WT) Arabidopsis plants that overexpressed LpSOS1, Under NaCl treatment,atsos1 and WT Arabidopsis plants overexpressing LpSOS1 exhibited better growth, with higher biomass, root length, and lateral root quantity, whereas in the absence of LpSOS1 overexpression, the plants of both lines were wilted and chlorotic and even died under salt stress. When exposed to salt stress, the expression of stress-related genes was notably upregulated in the LpSOS1 overexpression line of Arabidopsis as compared to the WT. Our findings indicate that LpSOS1 enhances salt tolerance in plants by regulating ion homeostasis, reducing Na+/K+ ratio, thereby protecting the plasma membrane from oxidative damage caused by salt stress, and enhancing the activity of antioxidant enzymes. Therefore, the increased salt tolerance conferred by LpSOS1 in plants makes it a potential bioresource for breeding salt-tolerant crops. Further investigation into the mechanisms underlying lily's resistance to salt stress would be advantageous and could serve as a foundation for future molecular improvements.


Assuntos
Arabidopsis , Lilium , Tolerância ao Sal/genética , Lilium/genética , Plantas Geneticamente Modificadas/metabolismo , Arabidopsis/metabolismo , Antiporters/genética , Antioxidantes , Cloreto de Sódio/farmacologia , Cloreto de Sódio/metabolismo , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Melhoramento Vegetal , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
19.
Diagn Pathol ; 18(1): 25, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36803395

RESUMO

OBJECTIVES: Pseudomyogenic hemangioendothelioma (PHE) is a rare intermediate hemangioendothelioma. This article aims to study the clinicopathological features of PHE. METHODS: We collected the clinicopathological features of 10 new PHE, and examined their molecular pathological features by fluorescence in situ hybridization. In addition, we summarized and analyzed the pathological data of 189 reported cases. RESULTS: The case group consisted of six men and four women aged 12-83 years (median: 41 years). Five instances occurred in the limbs, three in the head and neck, and two in the trunk. Tumor tissues were composed of spindle cells and round or polygonal epithelioid cells, which were either arranged in sheets or interwoven, along with areas of transitional morphology. Scattered or patchy stromal neutrophil infiltration was observed. Tumor cells had abundant cytoplasm, and some contained vacuoles. The nuclei had mild to moderate atypia, with visible nucleoli, and mitosis was rare. PHE tissues diffusely expressed CD31 and ERG, but not CD34, Desmin, SOX-10, HHV8 or S100, while some samples expressed CKpan, FLI-1 and EMA. INI-1 stain is retained. The proliferation index of Ki-67 is 10-35%. Seven samples were detected by fluorescence in situ hybridization, six of which had breakages in FosB proto-oncogene (AP-1 transcription factor subunit). Two patients experienced recurrence; however, no metastasis or death occurred. CONCLUSIONS: PHE is a rare soft tissue vascular tumor, which has biologically borderline malignant potential, local recurrence, little metastasis, and good overall survival and prognosis. Immunomarkers and molecular detection are valuable for diagnosis.


Assuntos
Hemangioendotelioma Epitelioide , Hemangioendotelioma , Hemangioma , Lesões Pré-Cancerosas , Neoplasias de Tecidos Moles , Feminino , Humanos , Masculino , Biomarcadores Tumorais/genética , Hemangioendotelioma/diagnóstico , Hemangioendotelioma/patologia , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/genética , Hemangioendotelioma Epitelioide/patologia , Hibridização in Situ Fluorescente , Neoplasias de Tecidos Moles/patologia , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
20.
Cancer Imaging ; 23(1): 8, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653861

RESUMO

OBJECTIVES: To compare tumor size measurements using CT and MRI in pancreatic cancer (PC) patients with neoadjuvant therapy (NAT). METHODS: This study included 125 histologically confirmed PC patients who underwent NAT. The tumor sizes from CT and MRI before and after NAT were compared by using Bland-Altman analyses and intraclass correlation coefficients (ICCs). Variations in tumor size estimates between MRI and CT in relationship to different factors, including NAT methods (chemotherapy, chemoradiotherapy), tumor locations (head/neck, body/tail), tumor regression grade (TRG) levels (0-2, 3), N stages (N0, N1/N2) and tumor resection margin status (R0, R1), were further analysed. The McNemar test was used to compare the efficacy of NAT evaluations based on the CT and MRI measurements according to RECIST 1.1 criteria. RESULTS: There was no significant difference between the median tumor sizes from CT and MRI before and after NAT (P = 0.44 and 0.39, respectively). There was excellent agreement in tumor size between MRI and CT, with mean size differences and limits of agreement (LOAs) of 1.5 [-9.6 to 12.7] mm and 0.9 [-12.6 to 14.5] mm before NAT (ICC, 0.93) and after NAT (ICC, 0.91), respectively. For all the investigated factors, there was good or excellent correlation (ICC, 0.76 to 0.95) for tumor sizes between CT and MRI. There was no significant difference in the efficacy evaluation of NAT between CT and MRI measurements (P = 1.0). CONCLUSION: MRI and CT have similar performance in assessing PC tumor size before and after NAT.


Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas , Humanos , Critérios de Avaliação de Resposta em Tumores Sólidos , Terapia Neoadjuvante/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Estudos Retrospectivos , Neoplasias Pancreáticas
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