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1.
Funct Integr Genomics ; 24(3): 78, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38632141

RESUMO

Transcriptional factor HOXB9, a part of the HOX gene family, plays a crucial role in the development of diverse cancer types. This study aimed to elucidate the regulatory mechanism of HOXB9 on the proliferation and invasion of laryngeal squamous cell carcinoma (LSCC) cells to provide guidance for the development and prognosis of LSCC. The CRISPR/Cas9 method was employed in LSCC cell lines to knock out the HOXB9 gene and validate its effects on the proliferation, migration, invasion, and regulation of LSCC cells. CCK-8 and flow cytometry were used to detect cell viability and proliferation; Tunnel was used to detect cell apoptosis, and transwell was used to detect cell migration and invasion. The effect of HOXB9 on tumor growth was tested in nude mice. The downstream target genes regulated by HOXB9 were screened by microarray analysis and verified by Western blotting, immunohistochemistry, chromatin immunoprecipitation, and double-luciferase reporter assays. The current research investigated molecular pathways governed by HOXB9 in the development of LSCC. Additionally, both laboratory- and living-organism-based investigations revealed that disrupting the HOXB9 gene through the CRISPR/CAS9 mechanism restrained cellular growth, movement, and infiltration, while enhancing cellular apoptosis. Detailed analyses of LSCC cell strains and human LSCC samples revealed that HOXB9 promoted LSCC progression by directly elevating the transcriptional activity of MMP12. HOXB9 could influence changes in LSCC cell functions, and the mechanism of action might be exerted through its downstream target gene, MMP12.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Proteínas de Homeodomínio , Neoplasias Laríngeas , Metaloproteinase 12 da Matriz , Animais , Humanos , Camundongos , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Genes Homeobox , Neoplasias de Cabeça e Pescoço/genética , Proteínas de Homeodomínio/genética , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , Camundongos Nus , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
2.
Neuroscience ; 545: 111-124, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38492796

RESUMO

Armcx1 is a member of the ARMadillo repeat-Containing protein on the X chromosome (ARMCX) family, which is recognized to have evolutionary conserved roles in regulating mitochondrial transport and dynamics. Previous research has shown that Armcx1 is expressed at higher levels in mice after axotomy and in adult retinal ganglion cells after crush injury, and this protein increases neuronal survival and axonal regeneration. However, its role in traumatic brain injury (TBI) is unclear. Therefore, the aim of this study was to assess the expression of Armcx1 after TBI and to explore possible related mechanisms by which Armcx1 is involved in TBI. We used C57BL/6 male mice to model TBI and evaluated the role of Armcx1 in TBI by transfecting mice with Armcx1 small interfering RNA (siRNA) to inhibit Armcx1 expression 24 h before TBI modeling. Western blotting, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Nissl staining, transmission electron microscopy, adenosine triphosphate (ATP) level measurement, neuronal apoptosis analysis, neurological function scoring and the Morris water maze were performed. The results demonstrated that Armcx1 protein expression was elevated after TBI and that the Armcx1 protein was localized in neurons and astroglial cells in cortical tissue surrounding the injury site. In addition, inhibition of Armcx1 expression further led to impaired mitochondrial transport, abnormal morphology, reduced ATP levels, aggravation of neuronal apoptosis and neurological dysfunction, and decrease Miro1 expression. In conclusion, our findings indicate that Armcx1 may exert neuroprotective effects by ameliorating neurological injury after TBI through a mitochondrial transport pathway involving Miro1.


Assuntos
Proteínas do Domínio Armadillo , Lesões Encefálicas Traumáticas , Camundongos Endogâmicos C57BL , Mitocôndrias , Proteínas rho de Ligação ao GTP , Animais , Masculino , Camundongos , Trifosfato de Adenosina/metabolismo , Apoptose/fisiologia , Proteínas do Domínio Armadillo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Modelos Animais de Doenças , Aprendizagem em Labirinto/fisiologia , Mitocôndrias/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Proteínas rho de Ligação ao GTP/metabolismo
3.
Phytomedicine ; 126: 155254, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342016

RESUMO

BACKGROUND: The gut-brain axis (GBA) plays a central role in cerebral ischaemia-reperfusion injury (CIRI). Rhubarb, known for its purgative properties, has demonstrated protective effects against CIRI. However, it remains unclear whether this protective effect is achieved through the regulation of the GBA. AIM: This study aims to investigate the mechanism by which rhubarb extract improves CIRI by modulating the GBA pathway. METHODS: We identified the active components of rhubarb extract using LC-MS/MS. The model of middle cerebral artery occlusion (MCAO) was established to evaluate the effect of rhubarb extract. We conducted 16S rDNA sequencing and untargeted metabolomics to analyze intestinal contents. Additionally, we employed HE staining, TUNEL staining, western blot, and ELISA to assess intestinal barrier integrity. We measured the levels of inflammatory cytokines in serum via ELISA. We also examined blood-brain barrier (BBB) integrity using Evans blue (EB) penetration, transmission electron microscopy (TEM), western blot, and ELISA. Neurological function scores and TTC staining were utilized to evaluate neurological outcomes. RESULTS: We identified twenty-six active components in rhubarb. Rhubarb extract enhanced α-diversity, reduced the abundance of Enterobacteriaceae, and partially rectified metabolic disorders in CIRI rats. It also ameliorated pathological changes, increased the expressions of ZO-1, Occludin, and Claudin 1 in the colon, and reduced levels of LPS and d-lac in serum. Furthermore, it lowered the levels of IL-1ß, IL-6, IL-10, IL-17, and TNF-α in serum. Rhubarb extract mitigated BBB dysfunction, as evidenced by reduced EB penetration and improved hippocampal microstructure. It upregulated the expressions of ZO-1, Occludin, Claudin 1, while downregulating the expressions of TLR4, MyD88, and NF-κB. Similarly, rhubarb extract decreased the levels of IL-1ß, IL-6, and TNF-α in the hippocampus. Ultimately, it reduced neurological function scores and cerebral infarct volume. CONCLUSION: Rhubarb effectively treats CIRI, potentially by inhibiting harmful bacteria, correcting metabolic disorders, repairing intestinal barrier function, alleviating BBB dysfunction, and ultimately improving neurological outcomes.


Assuntos
Isquemia Encefálica , Doenças Metabólicas , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Rheum , Ratos , Animais , Neuroproteção , Rheum/metabolismo , Ocludina/metabolismo , Interleucina-6 , Fator de Necrose Tumoral alfa/genética , Eixo Encéfalo-Intestino , Cromatografia Líquida , Claudina-1 , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Espectrometria de Massas em Tandem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Azul Evans/uso terapêutico , Traumatismo por Reperfusão/metabolismo , Doenças Metabólicas/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico
4.
BMC Cardiovasc Disord ; 24(1): 56, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238677

RESUMO

BACKGROUND: Previous models for predicting delirium after cardiac surgery remained inadequate. This study aimed to develop and validate a machine learning-based prediction model for postoperative delirium (POD) in cardiac valve surgery patients. METHODS: The electronic medical information of the cardiac surgical intensive care unit (CSICU) was extracted from a tertiary and major referral hospital in southern China over 1 year, from June 2019 to June 2020. A total of 507 patients admitted to the CSICU after cardiac valve surgery were included in this study. Seven classical machine learning algorithms (Random Forest Classifier, Logistic Regression, Support Vector Machine Classifier, K-nearest Neighbors Classifier, Gaussian Naive Bayes, Gradient Boosting Decision Tree, and Perceptron.) were used to develop delirium prediction models under full (q = 31) and selected (q = 19) feature sets, respectively. RESULT: The Random Forest classifier performs exceptionally well in both feature datasets, with an Area Under the Curve (AUC) of 0.92 for the full feature dataset and an AUC of 0.86 for the selected feature dataset. Additionally, it achieves a relatively lower Expected Calibration Error (ECE) and the highest Average Precision (AP), with an AP of 0.80 for the full feature dataset and an AP of 0.73 for the selected feature dataset. To further evaluate the best-performing Random Forest classifier, SHAP (Shapley Additive Explanations) was used, and the importance matrix plot, scatter plots, and summary plots were generated. CONCLUSIONS: We established machine learning-based prediction models to predict POD in patients undergoing cardiac valve surgery. The random forest model has the best predictive performance in prediction and can help improve the prognosis of patients with POD.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Delírio do Despertar , Humanos , Registros Eletrônicos de Saúde , Teorema de Bayes , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Valvas Cardíacas , Aprendizado de Máquina
5.
Anal Biochem ; 688: 115474, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38286352

RESUMO

The aim of this study is to investigate the role of CFHR1 in bile duct carcinoma (BDC) and its mechanism of action, and we hope that our analysis and research will contribute to a better understanding of cholangiocarcinoma (BDC) disease genesis, progression and the development of new therapeutic strategies. The prognostic receiver operating characteristic curve of CFHR1 was generated using survival ROC. The ROC curve for CFHR1 showed that there is a correlation between CFHR1 expression and clinicopathological parameters and has an impact on poor prognosis. STRING was used to predict the protein-protein interaction network of the identified genes, and the Microenvironment Cell Populations counter algorithm was used to analyze immune cell infiltration within the BDC. The combined analysis showed that CFHR1 was found to be upregulated in BDC tissues, along with a total of 20 related differentially expressed genes (DEGs) (8 downregulated and 12 upregulated genes). Also, the results showed that the expression of CFHR1 is correlated with immune cell infiltration in tumor and immune cell markers in BDC (P < 0.05). In addition, we have verified experimentally the biological function of CFHR1. These findings suggest that CFHR1 may be a prognostic marker and a potential therapeutic target for BDC. Information regarding the detailed roles of CFHR1 in BDC could be valuable for improving the diagnosis and treatment of this rare cancer.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/genética , Biomarcadores , Prognóstico , Ductos Biliares Intra-Hepáticos/patologia , Microambiente Tumoral , Proteínas Inativadoras do Complemento C3b
6.
Food Chem ; 440: 137825, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38159321

RESUMO

The juice exudation of aquatic products oozes out during storage can influence storage quality. Herein, a novel basil essential oil liposome unidirectional water-conducting sustained-release preservation pads (BEOL/UCSP) were prepared with nylon mesh as water-conducting layer, basil essential oil liposome (BEOL) as sustained-release preservation layer, and diatomite and absorbent-cotton as water-absorbing layer. EL/UCSP, ß-CL/UCSP, and BEO/UCSP were prepared after BEOL was replaced by eugenol liposome, ß-caryophyllene liposome, and BEO. BEOL are microspheres with bilayer structure, had good storage stability, centrifugal stability, thermal stability, embedding capacity, sustained-release, and oxidation resistance, and the main components of preservatives had a synergistic effect on antibacterial properties. The pads without preservative can initially slow down quality deterioration. BEOL/UCSP can directionally absorb exudate and realize long-term sustained-release of preservative, has excellent antibacterial and antioxidant effect, and extended shelf life of Lateolabrax japonicus fillets from 6.0 days to 12.8 days. The BEOL/UCSP can provide technical theoretical support for preservation materials.


Assuntos
Ocimum basilicum , Óleos Voláteis , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Conservação de Alimentos , Ocimum basilicum/química , Lipossomos , Preparações de Ação Retardada , Peixes , Antibacterianos
7.
Cancer Gene Ther ; 30(11): 1530-1542, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37563362

RESUMO

Long noncoding RNAs (lncRNAs) play a key role in human cancer development; nevertheless, the effect of lncRNA LINC00665 on the progression of gastric cancer (GC) still unclear. In this study, we found that LINC00665 expression is upregulated in GC than normal gastric mucosa tissues and higher LINC00665 expression is associated with a poor prognosis in GC patients. Downregulated LINC00665 inhibited GC cells proliferation, invasion, and migration in vitro. Pulmonary metastasis animal models showed that downregulated LINC00665 could reduce the lung metastasis of GC in vivo. Tumor organoids were generated from human malignant GC tissues, downregulated LINC00665 could inhibit the growth of the organoids of GC tissues. Mechanistically, downregulated LINC00665 could inhibit GC cells EMT. RNA pulldown, RIP, and RIP-seq studies found that LINC00665 can bind to the transcription factor YBX1 and form a positive feed-forward loop. The luciferase reporter and CHIP results showed that YBX1 could regulate the transcriptional activity of Wnt3a, and downregulation of LINC00665 could block the activation of Wnt/ß-catenin signaling. In conclusion, our results identified a feedback loop between LINC00665 and YBX1 that activates Wnt/ß-catenin signaling, and it may be a potential therapeutic approach to suppress GC progression.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Animais , Humanos , Neoplasias Gástricas/patologia , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Via de Sinalização Wnt/genética , Proliferação de Células/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Proteína 1 de Ligação a Y-Box/genética
8.
Int J Biol Sci ; 19(5): 1382-1400, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37056932

RESUMO

Translation machinery associated 7 homolog (TMA7) is closely related to proliferation-related diseases. However, the function and regulatory mechanism of TMA7 in laryngeal squamous cell carcinoma (LSCC) remain unclear. The present study aimed to investigate the effect of TMA7 on the occurrence and development of LSCC and to study the mechanism of TMA7. TMA7 is upregulated in LSCC tissues and associated with poor prognosis. After TMA7 downregulation, the autophagy level was increased, and the proliferation, migration, and invasion of LSCC cells were inhibited. The m6A methylated reader IGF2BP3 enhanced the stability of TMA7 and reduced the level of autophagy. TMA7 interacted directly with UBA2. Furthermore, the activation of the IGF2BP3-regulated TMA7-UBA2-PI3K pathway is the primary mechanism by which TMA7 inhibits autophagy and promotes the progression of LSCC. The current study revealed that IGF2BP3-mediated TMA7 m6A modification promotes LSCC progression and cisplatin-resistance through UBA2-PI3K pathway, providing new insights into the autophagy-related mechanism, potential biomarkers, and therapeutic targets for LSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , Humanos , Autofagia/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Metilação , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/metabolismo , Proteínas de Ligação a RNA/metabolismo
9.
Int J Biol Macromol ; 237: 123932, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36894058

RESUMO

In this study, the coaxial nanofiber films were prepared by coaxial electrospinning technique with cinnamaldehyde (CMA) and tea polyphenol (TP) as core material and polylactic acid (PLA) as shell material, and to obtain food packaging materials with great physicochemical and antibacterial properties, zinc oxide (ZnO) sol were added into PLA, and ZnO/CMA/TP-PLA coaxial nanofiber films were prepared. Meanwhile, the microstructure and physicochemical properties were determined, and the antibacterial properties and mechanism were investigated with Shewanella putrefaciens (S. putrefaciens) as target. The results show that the ZnO sol makes the physicochemical properties and antibacterial properties of the coaxial nanofiber films improve. Among them, the 1.0 % ZnO/CMA/TP-PLA coaxial nanofibers have smooth and continuous uniform surfaces, and their encapsulation effect on CMA/TP and antibacterial properties are the optimal. The synergistic action of CMA/TP and ZnO sol cause severe depression and folding of the cell membrane of S. putrefaciens, makes cell membrane permeability increase and of intracellular materials spillage, interference the bacteriophage protein expression, and makes macromolecular protein degraded. In this study, the introduction of oxide sols into polymeric shell materials by in-situ synthesis technique can provide theoretical support and methodological guidance for the application of electrospinning technology in the field of food packaging.


Assuntos
Nanofibras , Shewanella putrefaciens , Óxido de Zinco , Nanofibras/química , Óxido de Zinco/química , Polifenóis , Poliésteres/química , Antibacterianos/química , Chá
10.
Front Cardiovasc Med ; 9: 962992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061544

RESUMO

Background: Low cardiac output syndrome (LCOS) is the most serious physiological abnormality with high mortality for patients after cardiac surgery. This study aimed to explore the multidimensional data of clinical features and outcomes to provide individualized care for patients with LCOS. Methods: The electronic medical information of the intensive care units (ICUs) was extracted from a tertiary hospital in South China. We included patients who were diagnosed with LCOS in the ICU database. We used the consensus clustering approach based on patient characteristics, laboratory data, and vital signs to identify LCOS subgroups. The consensus clustering method involves subsampling from a set of items, such as microarrays, and determines to cluster of specified cluster counts (k). The primary clinical outcome was in-hospital mortality and was compared between the clusters. Results: A total of 1,205 patients were included and divided into three clusters. Cluster 1 (n = 443) was defined as the low-risk group [in-hospital mortality =10.1%, odds ratio (OR) = 1]. Cluster 2 (n = 396) was defined as the medium-risk group [in-hospital mortality =25.0%, OR = 2.96 (95% CI = 1.97-4.46)]. Cluster 3 (n = 366) was defined as the high-risk group [in-hospital mortality =39.2%, OR = 5.75 (95% CI = 3.9-8.5)]. Conclusion: Patients with LCOS after cardiac surgery could be divided into three clusters and had different outcomes.

11.
Nat Commun ; 13(1): 5091, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042210

RESUMO

X-ray-induced photodynamic therapy utilizes penetrating X-rays to activate reactive oxygen species in deep tissues for cancer treatment, which combines the advantages of photodynamic therapy and radiotherapy. Conventional therapy usually requires heavy-metal-containing inorganic scintillators and organic photosensitizers to generate singlet oxygen. Here, we report a more convenient strategy for X-ray-induced photodynamic therapy based on a class of organic phosphorescence nanoscintillators, that act in a dual capacity as scintillators and photosensitizers. The resulting low dose of 0.4 Gy and negligible adverse effects demonstrate the great potential for the treatment of deep tumours. These findings provide an optional route that leverages the optical properties of purely organic scintillators for deep-tissue photodynamic therapy. Furthermore, these organic nanoscintillators offer an opportunity to expand applications in the fields of biomaterials and nanobiotechnology.


Assuntos
Fotoquimioterapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Radiografia , Oxigênio Singlete , Raios X
12.
Theory Biosci ; 141(3): 297-311, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35921025

RESUMO

Breast cancer stem cells (BCSCs) with the ability to self-renew and differentiate have been identified in primary breast cancer tissues and cell lines. The BCSCs are often resistant to traditional radiation and/or chemotherapies. Previous studies have also shown that successful therapy must eradicate cancer stem cells. The purpose of this paper is to develop a mathematical model with self-feedback mechanism to illustrate the issues regarding the difficulties of absolutely eliminating a breast cancer. In addition, we introduce the mechanism of the epithelial-mesenchymal transition (EMT) to investigate the influence of EMT on the effects of breast cancer growth and treatment. Results indicate that the EMT mechanism facilitates the growth of breast cancer and makes breast cancer more difficult to be cured. Therefore, targeting the signals involved in EMT can halt tumor progression in breast cancer. Finally, we apply the experimental data to carry out numerical simulations and validate our theoretical conclusions.


Assuntos
Neoplasias da Mama , Transição Epitelial-Mesenquimal , Retroalimentação , Feminino , Humanos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
13.
J Cell Mol Med ; 26(2): 385-398, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850551

RESUMO

It has been shown that N6-methyladenosine (m6A) modification is involved in the development of complex human diseases, especially in the development of cancer. Our research investigated the role and mechanism of the m6A modification of lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) in Laryngeal squamous cell carcinoma (LSCC) progression. Microarray analysis was used to quantitatively detect the m6A apparent transcriptional modification level of lncRNA in LSCC tissue. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), in situ hybridization (ISH) and quantitative real-time PCR (qRT-PCR) were used to examine the m6A modification and expression of KCNQ1OT1. In addition, in vivo and in vitro experiments have tested the effects of KCNQ1OT1 knockdown on the proliferation, invasion and metastasis of LSCC. Mechanically, we found the N6-methyladenosine (m6A) demethylase ALKBH5 mediates KCNQ1OT1 expression via an m6A-YTHDF2-dependent manner and KCNQ1OT1 could directly bind to HOXA9 to further regulate the proliferation, invasion and metastasis of LSCC cells. In general, our research indicates that ALKBH5-mediated m6A modification of KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9.


Assuntos
Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Humanos , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , Regulação para Cima/genética
14.
Reprod Biol ; 22(1): 100594, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34953312

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine gynecological disorder. Insulin resistance (IR) is a major cause of PCOS. Melatonin, a critical endogenous hormone, has beneficial effects on the female reproductive system. This study aims to investigate the molecular effect of melatonin on IR in human ovarian granulosa cells (GCs). Hormone levels of the subjects were determined through clinical examination. The expression levels of insulin receptor substrate (IRS)-1 and glucose transporter (GLUT4) in GCs from PCOS patients and a human granulosa cell line (SVOG) were examined using qRT-PCR and western blot. The IR cell model was established by inducing SVOG cells with palmitic acid (PA). IR was detected in GCs of PCOS patients and SVOG by measuring glucose content and glucose uptake. Cell viability and apoptosis levels were detected by CCK-8 assay and flow cytometry. PI3K/Akt pathway expression in SVOG was assessed by western blot. PCOS patients had higher levels of luteinizing hormone (LH), testosterone, and LH/follicle-stimulating hormone. PA decreased cell viability, promoted apoptosis, and reduced glucose uptake in SVOG cells. IRS-1 and GLUT4 mRNA and protein expression was downregulated, and glucose uptake capacity was reduced in PCOS GCs and SVOG cells. Melatonin significantly upregulated IRS-1 and GLUT4 expression, downregulated p-IRS-1 (Ser307), and improved glucose uptake in PCOS patients' GCs and SVOG cells. PA decreased PI3K and Akt phosphorylation, whereas melatonin increased p-PI3K and p-Akt levels. Melatonin can reduce IR in GCs and PA-induced SVOG cells via the PI3K/Akt signaling pathway, providing more evidence for treating polycystic ovary syndrome.


Assuntos
Resistência à Insulina , Melatonina , Síndrome do Ovário Policístico , Feminino , Células da Granulosa , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Síndrome do Ovário Policístico/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
15.
Artigo em Inglês | MEDLINE | ID: mdl-34899952

RESUMO

OBJECTIVE: To study the clinical efficacy of integrated traditional Chinese medicine (TCM) and Western medicine (WM) in treating endometrial cancer and the influence on ultrasound, magnetic resonance imaging (MRI), tumor markers, human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125). METHOD: A total of 152 cases of patients with endometrial carcinoma were randomly divided into two groups: the TCM + WM group and the WM group. The WM group was treated with megestrol acetate tablets, and the TCM + WM group was treated with Radix Astragali injection on the basis of the control group. The levels of inflammatory factors, HE4 and CA125 in serum, were detected using enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay. The characteristics of ultrasound images and MRI images were observed and recorded. Toxicity, side effects, and the 3-year cumulative survival rate after treatment were assessed. RESULTS: After treatment, the levels of interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in both groups decreased, and the decrease in the TCM + WM group was more obvious than that in the WM group. There were statistically significant differences between the two groups in lesion shape, boundary, blood flow signal, lesion diameter, resistance index (RI), echo, intima thickness, and muscle layer infiltration from transvaginal ultrasound images after treatment. The diameter, echo, boundary, shape, composition, and enhancement degree of lesions between the two groups have a significant difference. Moreover, the levels of serum HE4 and CA125 in both groups decreased after treatment, and the decrease in the TCM + WM group was more obvious than that in the WM group. There were statistically significant differences between the two groups in the occurrence of myelosuppression, abnormal liver function, decreased platelet number, gastrointestinal reactions, leukopenia, and cardiotoxicity. After three years of follow-up, the cumulative survival rate of the TCM + WM group was 76.32%, and the cumulative survival rate of the WM group was 57.89%. CONCLUSION: Radix Astragali injection combined with megestrol acetate tablets has obvious therapeutic effects against endometrial cancer. Through vaginal ultrasonography and MRI, it can significantly improve the size, shape, and blood flow signals of patients' lesions, reduce the level of serum inflammatory factors and tumor markers HE4 and CA125, reduce the incidence of toxic and side reactions, improve the patient's immunity, improve the patient's condition significantly, and prolong the survival time of patients.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34804176

RESUMO

BACKGROUND: As a traditional Chinese medicine tonic, Buzhong Yiqi decoction has the effects of invigorating Qi and lifting Yang. In this study, the effects of Buzhong Yiqi Shenge decoction combined with THP bladder perfusion on postoperative efficacy in bladder cancer were investigated. METHODS: A total of 70 cases of bladder cancer patients were divided into the experimental group and control group according to the random number table method, with 35 cases in each group. The control group was treated with THP bladder perfusion. The experimental group was treated with Buzhong Yiqi Shenge decoction on the basis of the control group. The number of urine white blood cells, VEGF level, the incidence of adverse reactions, and KPS score were compared between the two groups before and after treatment. RESULTS: After 3 and 6 months of therapy, the KPS score of the experimental group increased significantly compared with the control group. However, after 12 months of treatment, there was no difference in KPS scores between the two groups. Moreover, there was no significant variation in serum VEGF between two groups after 3 months of treatment. However, Buzhong Yiqi decoction notably reduced the level of VEGF after 6 months and 12 months. After 3 months, the urine white blood cell count was lower in the experimental group than in the control group. After 6 and 12 months, there was no difference in urine white blood cell count between the two groups. Furthermore, a total of 14 patients in two groups had reoccurrence after one year. Our results showed that there was no significant difference in postoperative recurrence rate between the experimental group and the control group. The occurrence rates of frequent and urgent urination, nausea/loss, and abnormal urine routine of appetite in the experimental group were significantly lower than those in the control group. But there was no difference in the occurrence rate of low heat, hematuria between the experimental group and the control group. CONCLUSION: Buzhong Yiqi decoction combined with THP bladder perfusion has no advantage in the short-term recurrence rate of bladder cancer patients. However, Buzhong Yiqi decoction can alleviate the symptoms of adverse reactions and improve the quality of life of patients.

17.
J Nanobiotechnology ; 19(1): 185, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134721

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) are the dominant factor leading to tumor metastasis. This study aims to investigate the effect of disparate sources of CTCs on the treatment and prognosis of patients with advanced tumors by analyzing the number and gene mutations change of CTCs in arterial and venous blood in patients with advanced tumors. RESULTS: A CTCs sorting system was constructed based on Vimentin-immunolipid magnetic balls (Vi-IMB) and EpCAM immunolipid magnetic balls (Ep-IMB). Results showed that the prepared Ep-IMB and Vi-IMB had lower cytotoxicity, better specificity and sensitivity. The number of arterial CTCs was higher than that of venous CTCs, with a statistically significant difference (P < 0.05). Moreover, the prognosis of the low positive group of total CTCs in arterial blood and venous blood was higher than that of the high positive group, with a statistical significance (P < 0.05). The genetic testing results showed that the targeted drug gene mutations in tissues, arterial CTCs and venous CTCs showed a complementary trend, indicating that there was heterogeneity among different tumor samples. CONCLUSIONS: CTCs in blood can be efficiently captured by the CTCs sorting system based on Vi-LMB/Ep-LMB, and CTCs detection in arterial blood can be utilized to more accurately evaluate the prognosis and predict postoperative progress. It is further confirmed that tumor samples from disparate sources are heterogeneous, providing a reference basis for gene mutation detection before clinical targeted drug treatment, and the detection of CTCs in arterial blood has more potential clinical application value. TRIAL REGISTRATION: The Ethics Committee of Putuo Hospital, PTEC-A-2019-18-1. Registered 24 September 2019.


Assuntos
Biomarcadores Tumorais/genética , Molécula de Adesão da Célula Epitelial/genética , Magnetismo , Células Neoplásicas Circulantes , Vimentina/genética , Linhagem Celular Tumoral , Molécula de Adesão da Célula Epitelial/química , Fluorescência , Humanos , Fenômenos Magnéticos , Mutação , Prognóstico , Vimentina/química
18.
Int J Biol Macromol ; 184: 739-749, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34174310

RESUMO

Polylactic acid (PLA) is a promising food packaging material with biocompatible, nontoxic and biodegradable. In order to reduce the deterioration of aquatic products caused by microorganisms, PLA coaxial nanofiber films with cinnamaldehyde (CMA), tea polyphenol (TP) and its composite as core materials were prepared by using coaxial electrospinning technology. Its microscopic morphology and structure were characterized separately, and its thermal stability, wettability and mechanical properties were determined. The antibacterial activity and antibacterial mechanism of nanofiber films were studied with Shewanella putrefaciens (S. putrefaciens) which is the dominant spoilage of aquatic products as the target of action. The results show that the CMA/TP (m/m = 2:5)-PLA coaxial nanofibers have small diameter, uniform distribution, smooth surface, no pores and fracture. At the same time, the film has strong hydrophobicity, good thermal stability and mechanical properties. Its antibacterial performance is better than that of single-core nanofiber films, which effectively destroys the cell membrane of S. putrefaciens, increases the permeability of cell membrane, and interferes with the synthesis and expression of its protein. The coaxial nanofiber films with CMA, TP and its composite as core material can be used as a fresh-keeping material with antibacterial properties, and has potential application value in the field of food preservation.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/síntese química , Poliésteres/química , Polifenóis/síntese química , Shewanella putrefaciens/efeitos dos fármacos , Chá/química , Acroleína/química , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Estabilidade de Medicamentos , Microbiologia de Alimentos , Embalagem de Alimentos , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Nanofibras , Polifenóis/química , Polifenóis/farmacologia
19.
ORL J Otorhinolaryngol Relat Spec ; 83(6): 464-470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33831864

RESUMO

INTRODUCTION: Laryngeal squamous cell carcinoma (LSCC) is diverse in its natural history and responsiveness to treatments. There is an urgent need to generate candidate biomarkers for the stratification and individualization of treatment to avoid overtreatment or inadequate treatment. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been identified as an oncogenic gene in multiple human tumors entitles, and dysregulation of NEAT1 was tightly linked to carcinogenesis and cancer progression. METHODS: One hundred two paraffin samples of LSCC patients were collected. Furthermore, in situ hybridization (ISH), Kaplan-Meier, and MTT were used to analyze the relationship between NEAT1 and the progress of LSCC. RESULTS: In this study, ISH revealed that NEAT1 was strongly expressed in the nucleus. The increased expression of NEAT1 was correlated with T grade, neck nodal metastasis, clinical stage, drinking history, or smoking history of LSCC. The Kaplan-Meier analysis indicated that patients with higher NEAT1 expression had a worse overall survival in LSCC patients. In addition, NEAT1 knockdown significantly inhibited the growth of LSCC cells. CONCLUSION: Together, these results suggested that NEAT1 involved in the progress of LSCC and might act as a tumor oncogenic gene. This study provides a potential new marker and target for gene therapy in the treatment of LSCC.


Assuntos
Neoplasias Laríngeas , RNA Longo não Codificante , Carcinoma de Células Escamosas de Cabeça e Pescoço , Biomarcadores Tumorais/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/patologia , Prognóstico , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
20.
J Nanobiotechnology ; 19(1): 64, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653352

RESUMO

BACKGROUND: Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy. METHODS: Novel gadolinium doped carbon dots (Gd@CDs) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2'-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of Gd@CDs, a nanoplatform based on Gd@CDs has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC. RESULTS: The as-synthesized Dox@IR825@Gd@CDs displayed favorable MRI ability in vivo. Upon NIR laser irradiation, Dox@IR825@Gd@CDs could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. Dox@IR825@Gd@CDs presented low toxicity and high photothermal chemotherapy efficiency. CONCLUSION: A noble theranostic nanoplatform (Dox@IR825@Gd@CDs) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC.


Assuntos
Carbono/química , Sistemas de Liberação de Medicamentos/métodos , Tratamento Farmacológico/métodos , Gadolínio/química , Lasers , Imageamento por Ressonância Magnética/métodos , Fototerapia/métodos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Terapia Combinada , Doxorrubicina , Portadores de Fármacos/química , Feminino , Humanos , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanoestruturas/química , Neoplasias de Mama Triplo Negativas/radioterapia , Ensaios Antitumorais Modelo de Xenoenxerto
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