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1.
Am J Reprod Immunol ; 91(4): e13847, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38661639

RESUMO

PROBLEM: Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disorder, presents considerable therapeutic challenges due to its complex and elusive pathophysiology. METHOD OF STUDY: We employed three machine learning algorithms to identify potential biomarkers within a training dataset, comprising GSE138518, GSE155489, and GSE193123. The diagnostic accuracy of these biomarkers was rigorously evaluated using a validation dataset using area under the curve (AUC) metrics. Further validation in clinical samples was conducted using PCR and immunofluorescence techniques. Additionally, we investigate the complex interplay among immune cells in PCOS using CIBERSORT to uncover the relationships between the identified biomarkers and various immune cell types. RESULTS: Our analysis identified ACSS2, LPIN1, and NR4A1 as key mitochondria-related biomarkers associated with PCOS. A notable difference was observed in the immune microenvironment between PCOS patients and healthy controls. In particular, LPIN1 exhibited a positive correlation with resting mast cells, whereas NR4A1 demonstrated a negative correlation with monocytes in PCOS patients. CONCLUSION: ACSS2, LPIN1, and NR4A1 emerge as PCOS-related diagnostic biomarkers and potential intervention targets, opening new avenues for the diagnosis and management of PCOS.


Assuntos
Biomarcadores , Mitocôndrias , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/imunologia , Síndrome do Ovário Policístico/metabolismo , Feminino , Biomarcadores/metabolismo , Mitocôndrias/metabolismo , Aprendizado de Máquina , Adulto , Mastócitos/imunologia , Mastócitos/metabolismo
2.
Sci Rep ; 14(1): 4459, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396064

RESUMO

As the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What's more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two groups showed different drug sensitivity. On the other hand, two distinct subclasses (C1 and C2) were identified based on the 6 SLC genes. CRC patients in the high-risk group and C1 subtype had a worse prognosis. Furthermore, we found and validated that SLC12A2 was steadily upregulated in CRC. A loss-of-function study showed that knockdown of SLC12A2 expression restrained proliferation and stemness of CRC cells while a gain-of-function study showed the contrary results. Hence, we provided a 6-SLC gene signature for prognosis prediction of CRC patients. At the same time, we identified that SLC12A2 could promote tumor progression in CRC, which may serve as a potential therapeutic target.


Assuntos
Neoplasias Colorretais , Membro 2 da Família 12 de Carreador de Soluto , Humanos , Algoritmos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Proteínas de Membrana Transportadoras , Fenótipo , Prognóstico
3.
Am J Physiol Cell Physiol ; 326(2): C429-C441, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38105757

RESUMO

Senile osteoporosis increases fracture risks. Bone marrow stromal cells (BMSCs) are sensitive to aging. Deep insights into BMSCs aging are vital to elucidate the mechanisms underlying age-related bone loss. Recent advances showed that osteoporosis is associated with aberrant DNA methylation of many susceptible genes. Galectin-1 (Gal-1) has been proposed as a mediator of BMSCs functions. In our previous study, we showed that Gal-1 was downregulated in aged BMSCs and global deletion of Gal-1 in mice caused bone loss via impaired osteogenesis potential of BMSCs. Gal-1 promoter is featured by CpG islands. However, there are no reports concerning the DNA methylation status in Gal-1 promoter during osteoporosis. In the current study, we sought to investigate the role of DNA methylation in Gal-1 downregulation in aged BMSCs. The potential for anti-bone loss therapy based on modulating DNA methylation is explored. Our results showed that Dnmt3b-mediated Gal-1 promoter DNA hypermethylation plays an important role in Gal-1 downregulation in aged BMSCs, which inhibited ß-catenin binding on Gal-1 promoter. Bone loss of aged mice was alleviated in response to in vivo deletion of Dnmt3b from BMSCs. Finally, when bone marrow of young wild-type (WT) mice or young Dnmt3bPrx1-Cre mice was transplanted into aged WT mice, Gal-1 level in serum and trabecular bone mass were elevated in recipient aged WT mice. Our study will benefit for deeper insights into the regulation mechanisms of Gal-1 expression in BMSCs during osteoporosis development, and for the discovery of new therapeutic targets for osteoporosis via modulating DNA methylation status.NEW & NOTEWORTHY There is Dnmt3b-mediated DNA methylation in Gal-1 promoter in aged bone marrow stromal cell (BMSC). DNA methylation causes Gal-1 downregulation and osteogenesis attenuation of aged BMSC. DNA methylation blocks ß-catenin binding on Gal-1 promoter. Bone loss of aged mice is alleviated by in vivo deletion of Dnmt3b from BMSC.


Assuntos
Benzamidas , Células-Tronco Mesenquimais , Osteoporose , Tirosina/análogos & derivados , Animais , Camundongos , Metilação de DNA/genética , beta Catenina/metabolismo , Galectina 1/genética , Galectina 1/metabolismo , Osteogênese/genética , Osteoporose/genética , Osteoporose/metabolismo , Células-Tronco Mesenquimais/metabolismo , Regiões Promotoras Genéticas/genética , Diferenciação Celular , Células da Medula Óssea/metabolismo
4.
Biomed Pharmacother ; 166: 115340, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37625321

RESUMO

Ginsenosides, agents extracted from an important herb (ginseng), are expected to provide new therapies for endometrium-related diseases. Based on the molecular types of ginsenosides, we reviewed the main pharmacological effects of ginsenosides against endometrium-related diseases (e.g., endometrial cancers, endometriosis, and endometritis). The mechanism of action of ginsenosides involves inducing apoptosis of endometrium-related cells, promoting autophagy of endometrium-related cells, regulating epithelial-mesenchymal transition (EMT) in endometrium-related cells, and activating the immune system to kill cells associated with endometrial diseases. We hope to provide a theoretical foundation for the treatment of endometrium-related diseases by ginsenosides.


Assuntos
Neoplasias do Endométrio , Endometriose , Ginsenosídeos , Doenças Uterinas , Feminino , Humanos , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Endométrio , Neoplasias do Endométrio/tratamento farmacológico , Endometriose/tratamento farmacológico
5.
Zhongguo Gu Shang ; 36(3): 284-8, 2023 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-36946025

RESUMO

OBJECTIVE: To provide guidance for hip replacement by analyzing the variation of femoral head rotation center in different hip diseases. METHODS: A total of 5 459 patients were collected from March 2016 to June 2021, who took positive and proportional plain films of both hips for various reasons. The relative position between the rotation center of the femoral head and the apex of the greater trochanter was measured. The positive variation is more than 2 mm above the top of the great trochanter, and the negative variation is more than 2 mm below the top of the great trochanter. A total of 831 patients with variation of femoral head rotation center were collected and were divided into 4 groups according to different diseases, and the variation was counted respectively. There were 15 cases in the normal group involving 10 cases of positive variation and 5 cases of negative variation. There were 145 cases of avascular necrosis of femoral head involving 25 cases of positive variation and 120 cases of negative variation. There were 346 cases of congenital hip dysplasia involving 225 cases of positive variation(including 25 cases of typeⅠ, 70 cases of type Ⅱ, 115 cases of type Ⅲ and 15 cases of type Ⅳ), and 121 cases of negative variation(including 50 cases of crowe typeⅠ, 60 cases of typeⅡ, 10 cases of type Ⅲ and 1 case of type Ⅳ). There were 325 cases of hip osteoarthritis group involving 45 cases of positive variation and 280 cases of negative variation. RESULTS: There was significant difference in variation of femoral head rotation center among the four groups(P<0.05). There was significant difference in variation of femoral head rotation center among different types of congenital hip dysplasia(P<0.05). There were significant differences in cervical trunk angle and eccentricity among different variations of femoral head rotation center(P<0.05). CONCLUSION: The variation of femoral head rotation center is related to cervical trunk angle and eccentricity. The variation of femoral head rotation center is an important factor in hip diseases. The variation of femoral head rotation center is different in different hip diseases. Avascular necrosis of the femoral head and osteoarthritis of the hip were mostly negative variations. With the aggravation of congenital hip dysplasia, the variation of femoral head rotation center gradually changed from negative variation to positive variation.The variation of femoral head rotation center should be paid attention to in the preoperative planning of hip arthroplasty. It is of great significance to select the appropriate prosthesis and place the prosthesis accurately.


Assuntos
Artroplastia de Quadril , Luxação Congênita de Quadril , Prótese de Quadril , Humanos , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Luxação Congênita de Quadril/cirurgia , Artroplastia de Quadril/métodos , Fêmur/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
Front Immunol ; 13: 1022850, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479126

RESUMO

Background: The ulcerative colitis (UC) and Crohn's disease (CD) subtypes of inflammatory bowel disease (IBD) are autoimmune diseases influenced by multiple complex factors. The clinical treatment strategies for UC and CD often differ, indicating the importance of improving their discrimination. Methods: Two methods, robust rank aggregation (RRA) analysis and merging and intersection, were applied to integrate data from multiple IBD cohorts, and the identified differentially expressed genes (DEGs) were used to establish a protein-protein interaction (PPI) network. Molecular complex detection (MCODE) was used to identify important gene sets. Two differential diagnostic models to distinguish CD and UC were established via a least absolute shrinkage and selection operator (LASSO) logistic regression, and model evaluation was performed in both the training and testing groups, including receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis (DCA). The potential value of MMP-associated genes was further verified using different IBD cohorts and clinical samples. Results: Four datasets (GSE75214, GSE10616, GSE36807, and GSE9686) were included in the analysis. Both data integration methods indicated that the activation of the MMP-associated module was significantly elevated in UC. Two LASSO models based on continuous variable (Model_1) and binary variable (Model_2) MMP-associated genes were established to discriminate CD and UC. The results showed that Model_1 exhibited good discrimination in the training and testing groups. The calibration analysis and DCA showed that Model_1 exhibited good performance in the training group but failed in the testing group. Model_2 exhibited good discrimination, calibration and DCA results in the training and testing groups and exhibited greater diagnostic value. The effects of Model_1 and Model_2 were further verified in a new IBD cohort of GSE179285. The MMP genes exhibited high value as biomarkers for the discrimination of IBD patients using published cohort and immunohistochemistry (IHC) staining data. The MMP-associated gene levels were statistically significantly positively correlated with the levels of the differentially expressed cell types, indicating their potential value in differential diagnosis. The single-cell analysis confirmed that the expression of ANXA1 in UC was higher than that in CD. Conclusion: MMP-associated modules are the main differential gene sets between CD and UC. The established Model_2 overcomes batch differences and has good clinical applicability. Subsequent in-depth research investigating how MMPs are involved in the development of different IBD subtypes is necessary.


Assuntos
Colite Ulcerativa , Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/genética , Metaloproteinases da Matriz , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética
7.
Eur J Pharmacol ; 925: 174989, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35490722

RESUMO

Scabertopin (SCP), an abundant germacrane-type sesquiterpene lactone (SLC) isolated from Elephantopus scaber, was selected as a reference compound for modification and evaluation as anticancer agents for non-small cell lung cancer (NSCLC) treatment. All derivatives (SCP-1-SCP-13) except for SCP-3 showed potential inhibitory effect (IC50 5.2-9.7 µM) against A549 cells. The most promising compound SCP-7 also showed good cytotoxic activity against another two NSCLC cell lines (H1299 and H460), with IC50 value of 4.4 and 8.9 µM, respectively. Furthermore, SCP-7 could induce apoptotic cell death that was associated with the increased reactive oxygen species (ROS) generation, the loss of mitochondrial membrane potential, Bcl-2 family proteins modulation, caspases-3 and PARP cleavage. In addition, SCP-7 also inhibited cell growth by increasing Bax expression and reducing the Ki-67 positive cells in vivo, but there were no obvious toxic and side effects on internal organs. Mechanistically, PharmMapper, molecular docking and Western blot analysis revealed that SCP-7 might interact with the epidermal growth factor receptor (EGFR) and inhibit its expression in lung cancer cells. Together, above results suggest further effective application of SCP-7 as a potential anti-tumor agent in the treatment of NSCLC.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Humanos , Lactonas/farmacologia , Lactonas/uso terapêutico , Neoplasias Pulmonares/patologia , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos de Germacrano/farmacologia , Sesquiterpenos de Germacrano/uso terapêutico
8.
J Stomatol Oral Maxillofac Surg ; 123(6): e822-e827, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35257931

RESUMO

PURPOSE: To assess the false-positive and false-negative MRI results in evaluating the extent of tongue squamous cell carcinoma. METHODS: A prospective cohort series of 165 patients was enrolled to assess the false-positive and false-negative MRI results in evaluating the extent of tongue squamous cell carcinoma by comparing intraoperative tumor profile images and postoperative pathological sections. The differences between two-dimensional tumor margins were analyzed using Mimics 15.0 and Geomagic Control 16.0. A paired-samples t-test was used to analyze the agreement among MRI, intraoperative and pathological findings regarding the extent of tongue tumors. Multiple linear regression analysis was used to analyze associated factors. RESULTS: The mean and maximum false-positive values of pathological specimens was 1.95±1.39 mm (95% limit of agreement (LoA) 1.70-2.14) and 3.21 mm, respectively; the false-negative value was 0.44±0.49 mm. The false-positive value of intraoperative specimens was 1.52±0.87 mm (95% LoA 1.36-1.64); the false-negative value was 0.35±0.20 mm. Tumor morphology (ulcer type) (p<0.01) and depth of invasion (DOI) (≤5 mm) (p<0.01) were significantly correlated with the false-positive values of intraoperative and pathology specimens. CONCLUSION: The false-positive values are important when judging the invasion margin of tongue cancer and forming MRI-based operative plans; the false-negative value was almost negligible.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Língua , Humanos , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/cirurgia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Estudos Prospectivos , Prognóstico , Margens de Excisão , Imageamento por Ressonância Magnética/métodos , Estudos de Coortes , Língua/diagnóstico por imagem
9.
J Nat Prod ; 85(2): 352-364, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35090346

RESUMO

Two series of germacrane-type sesquiterpene lactones were produced by semisynthetic modulation of scaberol C, which was prepared by a standard chemical transformation from an Elephantopus scaber extract. Their inhibition activities against non-small-cell lung cancer cells were screened, and preliminary structure-activity relationships were also established. Among them, monomeric analog 1u and dimeric analog 3d exhibited superior anti-non-small-cell lung cancer cytotoxic potencies with IC50 values of 4.3 and 0.7 µM against A549 cells, respectively, and were more active than cisplatin and the standard sesquiterpene lactones, parthenolide and scabertopin. Further studies revealed that compounds 1u and 3d cause G2/M phase arrest and induce apoptosis through the activation of mitochondrial pathways in A549 cells. Collectively, the results obtained suggest that compounds 1u and 3d are promising anti-non-small-cell lung cancer lead compounds.


Assuntos
Antineoplásicos Fitogênicos , Asteraceae , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sesquiterpenos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Lactonas/química , Lactonas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Compostos Fitoquímicos , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/farmacologia
10.
World J Clin Cases ; 10(36): 13349-13355, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36683643

RESUMO

BACKGROUND: Pregnancy is a complex physiological process. Physiological leukocytosis occurs often and is mainly associated with increased neutrophil counts, especially in the third trimester of pregnancy. Non-congenital leukocytosis with white blood cell counts above 20 × 109/L lasting 13 wk during pregnancy is rare and has been reported occasionally. Herein, we present a case of pregnancy-induced leukocytosis. CASE SUMMARY: We present the case of a 33-year-old Chinese woman at 27 wk of gestation who had a leukocytosis complication. No abnormalities were detected in the examinations before pregnancy or in the first trimester. From the third trimester of pregnancy, the patient began to suffer from asymptomatic leukocytosis. We administered antibiotics to treat the patient; however, the complication persisted until the patient underwent a cesarean section after 40+3 wk of gestation. One day after the cesarean section, the patient's neutrophil count returned to normal. After 2 years of follow-up, we found that the patient and baby were healthy. CONCLUSION: Pregnancy-induced leukocytosis seems to be associated with immunoregulation and pregnancy termination may be the most effective treatment approach for pregnancies complicated with malignant leukocytosis.

11.
Int J Ophthalmol ; 14(11): 1653-1659, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804853

RESUMO

AIM: To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane (rhNGF-AM) on corneal epithelial and nerve regeneration in rabbit model. METHODS: Freshly prepared human amniotic membrane (AM) were immersed into PBS buffer containing 100 or 500 µg/mL rhNGF for 15, 30, and 60min at 4°C. The in vitro release kinetics of rhNGF was measured with ELISA. For in vivo evaluation, the AM were immersed with 500 µg/mL rhNGF for 30min. Fifty-seven rabbits were selected to establish corneal epithelial defect model. In addition to the 19 rabbits in control group, 38 rabbits received AM transplantation with or without rhNGF after the removal of central epithelium. Corneal epithelial defect area, sub-epithelial nerve fiber density, corneal sensitivity, rhNGF contents in resident AM and corneas were measured after the surgery. RESULTS: rhNGF was sustained release from the AM within 14d in vitro, with the positive correlation with initial immersion concentration. The immersion of AM in 500 µg/mL rhNGF for 30min achieved the most stable release within 14d. After transplantation in rabbit cornea, a high concentration of rhNGF in resident rhNGF-AM and cornea was maintained within 8d. Corneal epithelial healing, nerve fiber regeneration and the recovery of corneal sensitivity were significantly accelerated after the rhNGF-AM transplantation when compared to simple AM transplantation (all P<0.05). CONCLUSION: Simple immersion of AM achieves the sustained release of rhNGF, and promotes corneal epithelial wound healing and nerve regeneration, as well as the recovery of corneal sensitivity in rabbit.

12.
Biomed Res Int ; 2021: 6657767, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33869632

RESUMO

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common oral cancer and has a poor prognosis. We aimed to identify new biomarkers or potential therapeutic targets for OSCC. MATERIALS AND METHODS: Four pairs of tumor and adjacent normal tissues were collected from OSCC patients, and differentially expressed genes (DEGs) were screened via high-throughput RNA sequencing (RNA-seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to analyze the DEGs. A protein-protein interaction (PPI) network was established with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape, and two significant clusters were found. Candidate genes were screened by analyzing head and neck squamous cell carcinoma (HNSCC) data from The Cancer Genome Atlas (TCGA). A DEG-based risk model was established to predict the overall survival (OS) of OSCC patients via Kaplan-Meier analysis and the log-rank test. Furthermore, univariate Cox regression analysis was applied to assess associations between potential biomarkers and the overall survival rate. RESULTS: Of 720 total DEGs, fifty-two DEGs in the two subclusters of the PPI network analysis were selected. A risk model was established, and five candidate genes (SPRR2E, ICOS, CTLA4, HTR1D, and CCR4) were identified as biomarkers of OS in OSCC patients. CONCLUSIONS: We successfully constructed a prognostic signature to predict prognosis and identified five candidate genes associated with the OS of OSCC patients that are potential tumor biomarkers and targets in OSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Biologia Computacional , Perfilação da Expressão Gênica , Neoplasias Bucais/genética , Análise de Sequência de RNA , Carcinoma de Células Escamosas/patologia , Análise por Conglomerados , Feminino , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Estudos de Associação Genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Análise Multivariada , Prognóstico , Mapas de Interação de Proteínas/genética , Curva ROC , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Análise de Sobrevida , Transcrição Gênica
13.
J Asian Nat Prod Res ; 23(3): 217-227, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32102545

RESUMO

Four new alkaloids (1-4) and one known alkaloid were isolated from the stems of Picrasma quassioides. The structures of these isolated compounds were elucidated by spectroscopic analyses, a combination of computer-assisted structure elucidation software (ACD/Structure Elucidator) and gauge-including atomic orbital (GIAO) calculation of 1 D NMR data. All compounds were evaluated for their cytotoxic activities against hepatocellular carcinoma HepG2 and Hep3B cells. However, they did not show obvious inhibitory activities.[Figure: see text].


Assuntos
Alcaloides , Neoplasias Hepáticas , Picrasma , Alcaloides/farmacologia , Computadores , Humanos , Estrutura Molecular
14.
Nat Prod Res ; 35(14): 2454-2457, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31612726

RESUMO

Three new aromatic compounds (1a/1b, 2) including a pair of enantiomers (1a/1b), were isolated from Inonotus obliquus. The structures of the new compounds were elucidated by extensive spectroscopic analyses, and the absolute configurations of 1a and 1b were determined by electronic circular dichroism (ECD) calculated. All isolates were evaluated for their cytotoxic activities against Hep3B and HepG2 cell lines. Compounds 1b and 2 showed weak cytotoxicity toward the Hep3B cells at 25 µM.


Assuntos
Produtos Biológicos/isolamento & purificação , Inonotus/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Produtos Biológicos/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Dicroísmo Circular , Células Hep G2 , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Estereoisomerismo
15.
Bioorg Chem ; 104: 104314, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33011538

RESUMO

Small molecule accurate recognition technology (SMART) is an emerging method for the rapid structural prediction of major constituents from crude extracts and fractions. In the present study, a targeted isolation of an Elephantopus scaber extract by SMART resulted in the obtention of 15 new (1-15) and five known germacranolide sesquiterpenes (16-20). Their structures were assigned by extensively analyzing HRESIMS, NMR, X-ray crystallographic analyses, modified Mosher's method results, and quantum chemical calculate electronic circular dichroism (ECD) spectra. All germacranolide sesquiterpenes were screened to determine their inhibitory effects with two hepatoma cell lines (HepG2 and Hep3B), and compounds 14, 16, 18, 19 and 20 showed significant cytotoxic activities against the HepG2 (IC50, 3.3-9.9 µM) and Hep3B (IC50, 4.5-8.6 µM) cell lines. Further study suggested that 18 can induce the apoptosis of hepatoma cells via mitochondrial dysfunction.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Extratos Vegetais/farmacologia , Sesquiterpenos de Germacrano/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/isolamento & purificação , Relação Estrutura-Atividade
16.
Orphanet J Rare Dis ; 15(1): 227, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867823

RESUMO

BACKGROUND: Keratoconus (KC) is a common, degenerative disorder of the cornea, and genetic factors play a key role in its development. However, the genetic etiology of KC is still unclear. This study used the family of twins as material, using, for the first time, multi-omics analysis, to systematically display the changes in KC candidate factors in patients at the DNA, RNA, and protein levels. These can evaluate candidate pathogenic factors in depth and lock onto pathogenic targets. RESULTS: The twins in this study presented classic phenotypes, clear diagnoses, complete case data, and clinical samples, which are excellent materials for genetically studying KC. Whole-exome sequencing was conducted on both the twins and their parents. Transcriptome sequencing was conducted on proband's and health individual's primary human corneal fibroblast cells. Quantitative Real-time PCR and western blot were used to validate the differential gene expressions between the proband and controls. By integrating genomics, transcriptome, and protein level data, multiple consecutive events of KC were systematically analyzed to help better understand the molecular mechanism and genetic basis of KC. The results showed that the accumulation of rare, micro-effect risk variants was the pathogenic factor in this Chinese KC family. Consistent changes in extracellular matrices (ECMs) at the DNA and RNA levels suggested that ECM related changes play a key role in KC pathogenesis. The major gene variants (WNT16, CD248, COL6A2, COL4A3 and ADAMTS3) may affect the expression of related collagens or ECM proteins, thus reducing the amount of ECM in corneas and resulting in KC. CONCLUSIONS: This study, the first to explore the genetic etiology of KC via multi-omics analysis under the polygenetic model, has provided new insights into the genetic mechanisms underlying KC and an effective strategy for studying KC pathogenesis in the future.


Assuntos
Ceratocone , Antígenos CD , Antígenos de Neoplasias , Córnea , Matriz Extracelular/genética , Proteínas da Matriz Extracelular/genética , Fibroblastos , Humanos , Ceratocone/genética
17.
Fitoterapia ; 143: 104559, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32199958

RESUMO

Four undescribed oxylipin vanillyl acetals with four stereogenic carbons were isolated from the herbs of Solanum lyratum. A comprehensive set of spectroscopic methods were used to elucidate the structures and relative configurations of 1-4. The absolute configurations of the naturally occurring compounds are assigned as 7S, 9'S, 10'S, 11'R at the site of six-membered cyclic acetal attachment by electronic circular dichroism (ECD) calculations and the modified Mosher's method. Compounds 1 and 3 displayed moderate selective inhibition against Hep3B and HepG2 cells, respectively. Further Annexin V-FITC/PI staining assay revealed that 1 and 3 might have inhibitory effects on hepatoma cells through induction of apoptosis.


Assuntos
Acetais/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Oxilipinas/farmacologia , Solanum/química , Acetais/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose , China , Células Hep G2 , Humanos , Estrutura Molecular , Oxilipinas/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
18.
Saudi J Gastroenterol ; 26(1): 13-19, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31898644

RESUMO

BACKGROUND/AIM: To study the impact of computer-aided detection (CADe) system on the detection rate of polyps and adenomas in colonoscopy. MATERIALS AND METHODS: A total of 1026 patients were prospectively randomly scheduled for colonoscopy with (the CADe group, CADe) or without (the control group, CON) the aid of the CADe system, together with visual notification and voice alarm, so as to compare the detection rate of polyp. RESULTS: Compared with group CON, the detection rate of adenomas increased in group CADe, the average number of adenomas increased, the number of small adenomas increased, the number of proliferative polyps increased, and the differences were statistically significant (P < 0.001), but the comparison for the number of larger adenomas showed no significant difference between the groups (P> 0.05). CONCLUSIONS: The CADe system is feasible for increasing the detection of polyps and adenomas in colonoscopy.


Assuntos
Adenoma/diagnóstico , Inteligência Artificial/estatística & dados numéricos , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Adenoma/patologia , Adulto , Pólipos do Colo/patologia , Diagnóstico por Computador/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Fitoterapia ; 139: 104411, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31705951

RESUMO

Eleven sesquiterpenoids including four new eudesmane sesquiterpenoids, solanoids A-D (1-4), and seven known compounds (5-11) were isolated from the herbs of Solanum lyratum. By analyzing the UV, MS and NMR data, the gross structures of all isolates were established. The absolute configurations of these new compounds were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro cytotoxicity of all isolates against the hepatocellular carcinoma Hep3B and HepG2 cell lines was evaluated. Among them, compounds 7 and 11 exhibited moderate cytotoxicity against two cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Sesquiterpenos de Eudesmano/farmacologia , Solanum/química , Antineoplásicos Fitogênicos/isolamento & purificação , China , Células Hep G2 , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Sesquiterpenos de Eudesmano/isolamento & purificação
20.
Bioorg Chem ; 93: 103354, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31629256

RESUMO

Eleven aromatic compounds, including four pairs of undescribed phenylpropanoids and two undescribed dibenzofurans (1a/1b-4a/4b and 5-6), were isolated from the fruits of C. pinnatifida. Their structures were established by extensive spectroscopic analyses. Their relative and absolute configurations were determined by the assistance of quantum chemical calculations of NMR chemical shifts and electronic circular dichroism (ECD). All isolates were screened for the cytotoxicity against two human hepatoma cell lines, HepG2 and Hep3B. It was found that compound 7 exhibited noticeable cytotoxicity against both cells with the IC50 values of 12.24 (HepG2) and 24.90 (Hep3B) µM. Further Annexin VFITC/ PI staining assay suggested that 7 could induce apoptosis in a concentration-dependent manner to exert antiproliferative activities on hepatoma cells.


Assuntos
Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Crataegus/química , Dibenzofuranos/isolamento & purificação , Neoplasias Hepáticas/patologia , Propionatos/isolamento & purificação , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Células Hep G2 , Humanos , Espectroscopia de Prótons por Ressonância Magnética
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